N-(3-carbamoylphenly)-1h-pyrazole-5-carboxamide derivatives and the use thereof for controlling animal pests

ABSTRACT

The invention relates to compounds of the general formula (I) 
     
       
         
         
             
             
         
       
     
     in which the radicals A 1 , A 2 , A 3 , A 4 , L, Q, R 1 , T and W have the meaning given in the description and to the use of the compounds for controlling animal pests. The invention furthermore relates to processes and intermediates for preparing the compounds of formula (I).

The present application relates to novel halogen-substituted compounds,to processes for their preparation and to their use for controllinganimal pests, in particular arthropods and especially insects, arachnidsand nematodes.

It is known that certain halogen-substituted compounds have herbicidalaction (cf. J. Org. Chem. 1997, 62(17), 5908-5919, J. Heterocycl. Chem.1998, 35(6), 1493-1499, WO 2004/035545, WO 2004/106324, US 2006/069132,WO 2008/029084).

Furthermore, it is known that certain halogen-substituted compounds areinsecticidally active (EP1911751).

In addition, it is known that certain halogen-substituted compounds havecytokine-inhibitory activities (WO 00/07980).

Modern crop protection compositions have to meet many demands, forexample in relation to efficacy, persistence and spectrum of theiraction and possible use. Questions of toxicity, the combinability withother active compounds or formulation auxiliaries play a role, as wellas the question of the expense that the synthesis of an active compoundrequires. Furthermore, resistances may occur. For all these reasons, thesearch for novel crop protection agents can never be considered ashaving been concluded, and there is a constant need for novel compoundshaving properties which, compared to the known compounds, are improvedat least in respect of individual aspects.

It was an object of the present invention to provide compounds whichwiden the spectrum of the pesticides under various aspects and/orimprove their activity.

Surprisingly, it has now been found that certain halogen-substitutedcompounds and their N-oxides and salts have biological properties andare particularly suitable for controlling animal pests, and cantherefore be employed particularly well in the agrochemical field and inthe animal health sector.

Similar compounds are already known from WO 2010/051926.

The halogen-substituted compounds according to the invention are definedby the general formula (I)

in which

-   R¹ represents hydrogen, optionally substituted C₁-C₆-alkyl,    C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₇-cycloalkyl, C₁-C₆-alkylcarbonyl,    C₁-C₆-alkoxycarbonyl, cyano-C₁-C₂-alkyl, aryl-(C₁-C₃)-alkyl,    heteroaryl-(C₁-C₃)-alkyl,    the chemical grouping-   A₁ represents CR² or nitrogen,-   A₂ represents CR³ or nitrogen,-   A₃ represents CR⁴ or nitrogen and-   A₄ represents CR⁵ or nitrogen, but where not more than three of the    chemical groupings A₁ to A₄ simultaneously represent nitrogen;-   R², R³, R⁴ and R⁵ independently of one another represent hydrogen,    halogen, CN, NO₂, optionally substituted C₁-C₆-alkyl,    C₁-C₆-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl,    C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio,    C₁-C₆-haloalkylthio, C₁-C₆-alkylsulphinyl, C₁-C₆-haloalkylsulphinyl,    C₁-C₆-alkylsulphonyl, C₁-C₆-haloalkylsulphonyl, C₁-C₆-alkylamino,    N,N-di-C₁-C₆alkylamino, N—C₁-C₆-alkylaminocarbonyl,    N—C₃-C₆-cycloalkylaminocarbonyl or (C₁-C₃-alkoxy)carbonyl;    -   if none of the groupings A₂ and A₃ represents nitrogen, R³ and        R⁴ together with the carbon atom to which they are attached may        form a 5- or 6-membered ring which contains 0, 1 or 2 nitrogen        atoms and/or 0 or 1 oxygen atom and/or 0 or 1 sulphur atom, or    -   if none of the groupings A₁ and A₂ represents nitrogen, R² and        R³ together with the carbon atom to which they are attached may        form a 6-membered ring which contains 0, 1 or 2 nitrogen atoms;-   W represents oxygen or sulphur;-   R⁶ represents hydrogen, optionally substituted C₁-C₆-alkyl,    aryl-(C₁-C₃)-alkyl, heteroaryl-(C₁-C₃)-alkyl, C₂-C₆-alkenyl,    C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, (C₁-C₃-alkyl)-C₃-C₆-cycloalkyl and    (C₃-C₆-cycloalkyl)-C₁-C₃-alkyl, C₁-C₆-alkylcarbonyl,    C₁-C₆-alkoxycarbonyl;-   Q represents

-   E represents a bond, —CH₂—, S, SO, SO₂, —S—CH₂—, —SO—CH₂—,    —SO₂—CH₂—, —CH₂—S—CH₂—, —CH₂—SO—CH₂—, —CH₂—SO₂—CH₂—, —S—CH₂—CH₂—,    —SO—CH₂—CH₂—, —SO₂—CH₂—CH₂—, —NR⁶—CH₂—, —CH₂—NR⁶—CH₂—;-   R⁷ represents cyano or C(═S)NH₂;-   Z¹ represents optionally substituted C₁-C₆-haloalkyl or    C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, and-   Z² represents halogen, cyano, nitro or optionally substituted    C₁-C₆-haloalkyl, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio,    C₁-C₆-alkylsulphinyl, C₁-C₆-haloalkylsulphinyl,    C₁-C₆-alkylsulphonyl, C₁-C₆-haloalkylsulphonyl, and-   Z³ represents hydrogen or optionally substituted C₁-C₆-alkyl,    C₁-C₄-alkenyl, C₁-C₄-alkynyl, C₁-C₆-haloalkyl;

Preference is given to compounds of the formula (I)

in which

-   R¹ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl,    isobutyl, s-butyl, t-butyl, methoxymethyl, ethoxymethyl,    propoxymethyl, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl,    isopropylcarbonyl, s-butylcarbonyl, t-butylcarbonyl,    methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl,    isopropoxycarbonyl, s-butoxycarbonyl, t-butoxycarbonyl, cyanomethyl,    2-cyanoethyl, benzyl, 4-methoxybenzyl, pyrid-2-ylmethyl,    pyrid-3-ylmethyl, pyrid-4-ylmethyl, 4-chloropyrid-3-ylmethyl;    the chemical grouping-   A₁ represents CR² or nitrogen,-   A₂ represents CR³ or nitrogen,-   A₃ represents CR⁴ or nitrogen and-   A₄ represents CR⁵ or nitrogen,    but where not more than three of the chemical groupings A₁ to A₄    simultaneously represent nitrogen;-   R² and R⁵ independently of one another represent hydrogen, methyl,    fluorine or chlorine and-   R³ and R⁴ independently of one another represent hydrogen, fluorine,    chlorine, bromine, CN, NO₂, methyl, ethyl, fluoromethyl,    difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, methoxy,    ethoxy, n-propoxy, 1-methylethoxy, fluoromethoxy, difluoromethoxy,    chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy,    2,2,2-trifluoroethoxy, 2-chloro-2,2-difluoroethoxy,    pentafluoroethoxy, methyl sulphonyl, methylsulphinyl,    trifluoromethylsulphonyl, trifluoromethylsulphinyl; where-   W represents oxygen,-   R⁶ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl,    isobutyl, s-butyl, t-butyl, methoxymethyl, ethoxymethyl,    propoxymethyl, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl,    isopropylcarbonyl, s-butylcarbonyl, t-butylcarbonyl,    methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl,    isopropoxycarbonyl, s-butoxycarbonyl, t-butoxycarbonyl, cyanomethyl,    2-cyanoethyl, benzyl, 4-methoxybenzyl, pyrid-2-ylmethyl,    pyrid-3-ylmethyl, pyrid-4-ylmethyl, 4-chloropyrid-3-ylmethyl;-   Q represents

-   E represents a bond or —CH₂—;-   R⁷ represents cyano or C(═S)NH₂;-   Z¹ represents difluoromethyl, trichloromethyl, chlorodifluoromethyl,    dichlorofluoromethyl, trifluoromethyl, bromodichloromethyl,    chloromethyl, bromomethyl, 1-fluoroethyl, 1-fluoro-1-methylethyl,    2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,    1,2,2,2-tetrafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethyl,    2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl,    pentafluoroethyl, pentafluoro-t-butyl, heptafluoro-n-propyl,    heptafluoroisopropyl, nonafluoro-n-butyl, cyclopropyl,    1-chlorocyclopropyl, 1-fluorocyclopropyl, 1-bromocyclopropyl,    1-cyanocyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl or    2,2-difluoro-1-methylcyclopropyl, and-   Z² represents halogen, cyano, nitro, difluoromethyl,    trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl,    trifluoromethyl, bromodichloromethyl, chloromethyl, bromomethyl,    1-fluoroethyl, 1-fluoro-1-methylethyl, 2-fluoroethyl,    2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,2,2,2-tetrafluoroethyl,    1-chloro-1,2,2,2-tetrafluoroethyl, 2,2,2-trichloroethyl,    2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl, pentafluoroethyl,    pentafluoro-t-butyl, heptafluoro-n-propyl, heptafluoroisopropyl,    nonafluoro-n-butyl, methylthio, methylsulphinyl, methylsulphonyl,    ethylthio, ethylsulphinyl, ethylsulphonyl, trifluoromethylthio,    trifluoromethylsulphinyl, trifluoromethylsulphonyl, and-   Z³ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl,    isobutyl, s-butyl, t-butyl, ethenyl, 1-propenyl, 2-propenyl,    ethynyl, 1-propynyl, 1-butynyl, difluoromethyl, trichloromethyl,    chlorodifluoromethyl, dichlorofluoromethyl, trifluoromethyl,    chloromethyl, bromomethyl, 1-fluoroethyl, 1-fluoro-1-methylethyl,    2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl;

Further particularly preferred compounds are compounds of the generalformula (I) in which

-   Z¹ represents trifluoromethyl, 1-chlorocyclopropyl,    1-fluorocyclopropyl or pentafluoroethyl,-   Z² represents trifluoromethyl, nitro, methylthio, methylsulphinyl,    methylsulphonyl, fluorine, chlorine, bromine or iodine,-   Z³ represents methyl, ethyl, n-propyl or hydrogen,-   R¹ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl,    isobutyl, s-butyl, t-butyl, methoxymethyl, ethoxymethyl,    propoxymethyl, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl,    isopropylcarbonyl, s-butylcarbonyl, t-butylcarbonyl,    methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl,    isopropoxycarbonyl, s-butoxycarbonyl, t-butoxycarbonyl, cyanomethyl,    2-cyanoethyl, benzyl, 4-methoxybenzyl, pyrid-2-ylmethyl,    pyrid-3-ylmethyl, pyrid-4-ylmethyl, 4-chloropyrid-3-ylmethyl,-   A¹, A² and A⁴ represent CH,-   A₃ represents CR⁴ and-   R⁴ represents fluorine, chlorine, bromine or iodine,-   R⁶ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl,    isobutyl, s-butyl, t-butyl,-   W represents oxygen and-   Q represents 1-cyanocyclopropyl.

Preference is in particular given to further compounds in which

-   Z¹ represents trifluoromethyl, 1-chlorocyclopropyl,    1-fluorocyclopropyl or pentafluoroethyl,-   Z² represents trifluoromethyl, chlorine or-   Z³ represents methyl,-   R¹ represents hydrogen, methyl, ethyl,-   A¹, A² and A⁴ represent CH,-   A₃ represents CR⁴ and-   R⁴ represents chlorine,-   R⁶ represents hydrogen, methyl, ethyl,-   W represents oxygen and-   Q represents 1-cyanocyclopropyl.

The invention furthermore comprises novel compounds of the generalformulae (IVa), (IVb), (Va), (Vb) as preferred starting materials forthe synthesis of the compounds of the general formula (I).

The compounds of the general formulae (IVa) and (IVb) are preferredembodiments of the precursors of the general formula (IV) according toreaction schemes 1, 2 and 3, for example. The preparation of thecompounds of the general formula (I) is, inter alia, preferably carriedout using these compounds. The compounds of the general formula (IVb)are usually converted by reduction into the compounds (IVa).

The compounds (IVa) and (IVb) are defined by the general formulae below

in which

-   R², R³, R⁴ and R⁵ independently of one another represent hydrogen,    halogen, cyano, nitro, optionally substituted C₁-C₆-alkyl,    C₁-C₆-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl,    C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkylthio,    C₁-C₆-haloalkylthio, C₁-C₆-alkylsulphinyl, C₁-C₆-haloalkylsulphinyl,    C₁-C₆-alkylsulphonyl, C₁-C₆-haloalkylsulphonyl, C₁-C₆-alkylamino,    N,N-di-C₁-C₆-alkylamino, N—C₁-C₆-alkylaminocarbonyl,    N—C₃-C₆-cycloalkylaminocarbonyl or (C₁-C₃-alkoxy)carbonyl.

Preference is given to compounds of the general formulae (IVa), (IVb) inwhich

-   R² and R⁵ represent hydrogen or halogen, and-   R³ and R⁴ represent hydrogen, halogen, cyano, nitro, C₁-C₆-alkyl,    C₁-C₆-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl,    C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₁-C₆-alkylsulphinyl,    C₁-C₆-haloalkylsulphinyl, C₁-C₆-alkylsulphonyl,    C₁-C₆-haloalkylsulphonyl.

Particular preference is given to compounds of the general formulae(IVa), (IVb) in which

-   R² represents hydrogen or fluorine, and-   R³ represents hydrogen, fluorine, chlorine, bromine, iodine, cyano,    nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,    s-butyl, t-butyl, cyclopropyl, 1-chlorocyclopropyl,    1-fluorocyclopropyl, methylthio, trifluoromethylthio,    methylsulphinyl, trifluoromethylsulphinyl, methylsulphonyl,    trifluoromethylsulphonyl, and-   R⁴ represents hydrogen, fluorine, chlorine, bromine, iodine, cyano,    nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,    s-butyl, t-butyl, cyclopropyl, 1-chlorocyclopropyl,    1-fluorocyclopropyl, methylthio, trifluoromethylthio,    methylsulphinyl, trifluoromethylsulphinyl, methylsulphonyl,    trifluoromethylsulphonyl, and-   R⁵ represents hydrogen.

Very particular preference is given to compounds of the general formulae(IVa), (IVb) in which

-   R² and R⁵ represent hydrogen, and-   R³ represents hydrogen, fluorine, chlorine, bromine, iodine, cyano,    methyl, ethyl, methylthio, trifluoromethylthio, methylsulphinyl,    trifluoromethylsulphinyl, methylsulphonyl, trifluoromethylsulphonyl,    and-   R⁴ represents fluorine, chlorine, bromine, iodine, methyl, and-   R⁵ represents hydrogen.

The compounds of the general formulae (Va) and (Vb) are preferredembodiments of the precursors of the general formula (V) according toreaction schemes 1, 2 and 8, for example. The preparation of thecompounds of the general formula (I) is, inter alia, preferably carriedout using these compounds.

The compounds (Va) and (Vb) are defined by the general formulae below,in which

-   X¹ represents halogen, cyano and C₁-C₄-haloalkyl, and-   Z² represents halogen, cyano, nitro or optionally substituted    C₁-C₆-haloalkyl, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio,    C₁-C₆-alkylsulphinyl, C₁-C₆-haloalkylsulphinyl,    C₁-C₆-alkylsulphonyl, C₁-C₆-haloalkylsulphonyl, and-   Z³ represents hydrogen or optionally substituted C₁-C₆-alkyl,    C₁-C₄-alkenyl, C₁-C₄-alkynyl, C₁-C₆-haloalkyl, and-   Y represents optionally substituted C₁-C₆-alkyl.

Preference is given to compounds of the general formulae (Va) and (Vb)in which

-   X¹ represents fluorine, chlorine, bromine, cyano and    C₁-C₂-haloalkyl, and-   Z² represents halogen, cyano, nitro, difluoromethyl,    trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl,    trifluoromethyl, bromodichloromethyl, chloromethyl, bromomethyl,    1-fluoroethyl, 1-fluoro-1-methylethyl, 2-fluoroethyl,    2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,2,2,2-tetrafluoroethyl,    1-chloro-1,2,2,2-tetrafluoroethyl, 2,2,2-trichloroethyl,    2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl, pentafluoroethyl,    pentafluoro-t-butyl, heptafluoro-n-propyl, heptafluoroisopropyl,    nonafluoro-n-butyl, methylthio, methylsulphinyl, methylsulphonyl,    ethylthio, ethylsulphinyl, ethylsulphonyl, trifluoromethylthio,    trifluoromethylsulphinyl, trifluoromethylsulphonyl, and-   Z³ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl,    isobutyl, s-butyl, t-butyl, ethenyl, 1-propenyl, 2-propenyl,    ethynyl, 1-propynyl, 1-butynyl, difluoromethyl, trichloromethyl,    chlorodifluoromethyl, dichlorofluoromethyl, trifluoromethyl,    chloromethyl, bromomethyl, 1-fluoroethyl, 1-fluoro-1-methylethyl,    2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, and-   Y represents optionally substituted C₁-C₆-alkyl.

Particular preference is given to compounds of the general formulae (Va)and (Vb) in which

-   X¹ represents fluorine, chlorine, trifluoromethyl or    pentafluoroethyl, and-   Z² represents trifluoromethyl, nitro, methylthio, methylsulphinyl,    methylsulphonyl, fluorine, chlorine, bromine or iodine, and-   Z³ represents methyl, ethyl, n-propyl or hydrogen, and-   Y represents methyl, ethyl, n-propyl, isopropyl, n-butyl or t-butyl.

According to the invention, “alkyl”—on its own or as part of a chemicalgroup—represents straight-chain or branched hydrocarbons preferablyhaving 1 to 6 carbon atoms such as, for example, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl,1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl,1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl,1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,1,2-dimethylpropyl, 1,3-dimethylbutyl, 1,4-dimethylbutyl,2,3-dimethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl,3,3-dimethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl,1-ethylbutyl and 2-ethylbutyl. Preference is furthermore given to alkylgroups having 1 to 4 carbon atoms such as, inter alia, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, s-butyl or t-butyl. The alkylgroups according to the invention may be substituted by one or moreidentical or different radicals.

According to the invention, “alkenyl”—on its own or as part of achemical group—represents straight-chain or branched hydrocarbonspreferably having 2 to 6 carbon atoms and at least one double bond suchas, for example, vinyl, 2-propenyl, 2-butenyl, 3-butenyl,1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl,4-pentenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl,1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl,1,1-dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-2-propenyl,2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-2-pentenyl,2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl,3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl,2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl,1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-2-butenyl,1,2-dimethyl-3-butenyl, 1,3-dimethyl-2-butenyl, 2,2-dimethyl-3-butenyl,2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 1-ethyl-2-butenyl,1-ethyl-3-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl,1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl and1-ethyl-2-methyl-2-propenyl. Preference is furthermore given to alkenylgroups having 2 to 4 carbon atoms such as, inter alia, 2-propenyl,2-butenyl or 1-methyl-2-propenyl. The alkenyl groups according to theinvention may be substituted by one or more identical or differentradicals.

According to the invention, “alkynyl”—on its own or as part of achemical group—represents straight-chain or branched hydrocarbonspreferably having 2 to 6 carbon atoms and at least one triple bond suchas, for example, 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl,2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-3-butynyl,2-methyl-3-butynyl, 1-methyl-2-butynyl, 1,1-dimethyl-2-propynyl,1-ethyl-2-propynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl,1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl,2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl,4-methyl-2-pentynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl,2,2-dimethyl-3-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl,1-ethyl-1-methyl-2-propynyl and 2,5-hexadiynyl. Preference isfurthermore given to alkynyl groups having 2 to 4 carbon atoms such as,inter alia, ethynyl, 2-propynyl or 2-butynyl-2-propenyl. The alkynylgroups according to the invention may be substituted by one or moreidentical or different radicals.

According to the invention, “cycloalkyl”—on its own or as part of achemical group—represents mono-, bi- or tricyclic hydrocarbonspreferably having 3 to 10 carbons such as, for example, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl or adamantyl. Preference isfurthermore given to cycloalkyl groups having 3, 4, 5, 6 or 7 carbonatoms such as, inter alia, cyclopropyl or cyclobutyl. The cycloalkylgroups according to the invention may be substituted by one or moreidentical or different radicals.

According to the invention, “alkylcycloalkyl” represents mono-, bi- ortricyclic alkylcycloalkyl preferably having 4 to 10 or 4 to 7 carbonatoms such as, for example, ethylcyclopropyl, isopropylcyclobutyl,3-methylcyclopentyl and 4-methylcyclohexyl. Preference is furthermoregiven to alkylcycloalkyl groups having 4, 5 or 7 carbon atoms such as,inter alia, ethylcyclopropyl or 4-methylcyclohexyl. The alkylcycloalkylgroups according to the invention may be substituted by one or moreidentical or different radicals.

According to the invention, “cycloalkylalkyl” represents mono-, bi- ortricyclic cycloalkylalkyl preferably having 4 to 10 or 4 to 7 carbonatoms such as, for example, cyclopropylmethyl, cyclobutylmethyl,cyclopentylmethyl, cyclohexylmethyl and cyclopentylethyl. Preference isfurthermore given to cycloalkylalkyl groups having 4, 5 or 7 carbonatoms such as, inter alia, cyclopropylmethyl or cyclobutylmethyl. Thecycloalkylalkyl groups according to the invention may be substituted byone or more identical or different radicals.

According to the invention, “halogen” represents fluorine, chlorine,bromine or iodine, in particular fluorine, chlorine or bromine.

The halogen-substituted chemical groups according to the invention suchas, for example, haloalkyl, halocycloalkyl, haloalkyloxy, haloalkylthio,haloalkylsulphinyl or haloalkylsulphonyl are mono- or polysubstituted byhalogen up to the maximum possible number of substituents. In the caseof polysubstitution by halogen, the halogen atoms can be identical ordifferent, and can all be attached to one or to a plurality of carbonatoms. Here, halogen represents in particular fluorine, chlorine,bromine or iodine, preferably fluorine, chlorine or bromine andparticularly preferably fluorine.

According to the invention, “halocycloalkyl” represents mono-, bi- ortricyclic halocycloalkyl having preferably 3 to 10 carbon atoms such as,inter alia, 1-fluorocyclopropyl, 2-fluorocyclopropyl or1-fluorocyclobutyl. Preference is furthermore given to halocycloalkylhaving 3, 5 or 7 carbon atoms. The halocycloalkyl groups according tothe invention may be substituted by one or more identical or differentradicals.

According to the invention, “haloalkyl” “haloalkenyl” or “haloalkynyl”represents halogen-substituted alkyl, alkenyl or alkynyl groups havingpreferably 1 to 9 identical or different halogen atoms such as, forexample, monohaloalkyl such as CH₂CH₂Cl, CH₂CH₂F, CHClCH₃, CHFCH₃,CH₂Cl, CH₂F; perhaloalkyl such as CCl₃ or CF₃ or CF₂CF₃; polyhaloalkylsuch as CHF₂, CH₂F, CH₂CHFCl, CHCl₂, CF₂CF₂H, CH₂CF₃. This appliescorrespondingly to haloalkenyl and other halogen-substituted radicals.Haloalkoxy is, for example, OCF₃, OCHF₂, OCH₂F, OCF₂CF₃, OCH₂CF₃ andOCH₂CH₂Cl.

Further examples for haloalkyl groups are trichloromethyl,chlorodifluoromethyl, dichlorofluoromethyl, chloromethyl, bromomethyl,1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, pentafluoroethyl andpentafluoro-t-butyl. Preference is given to haloalkyl groups having 1 to4 carbon atoms and 1 to 9, preferably 1 to 5, identical or differenthalogen atoms selected from the group consisting of fluorine, chlorineand bromine. Particular preference is given to haloalkyl groups having 1or 2 carbon atoms and 1 to 5 identical or different halogen atomsselected from the group consisting of fluorine and chlorine such as,inter alia, difluoromethyl, trifluoromethyl or 2,2-difluoroethyl.

According to the invention, “hydroxyalkyl” represents a straight-chainor branched alcohol preferably having 1 to 6 carbon atoms such as, forexample, methanol, ethanol, n-propanol, isopropanol, n-butanol,isobutanol, s-butanol and t-butanol. Preference is furthermore given tohydroxyalkyl groups having 1 to 4 carbon atoms. The hydroxyalkyl groupsaccording to the invention may be substituted by one or more identicalor different radicals.

According to the invention, “alkoxy” represents a straight-chain orbranched O-alkyl preferably having 1 to 6 carbon atoms such as, forexample, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy,s-butoxy and t-butoxy. Preference is furthermore given to alkoxy groupshaving 1 to 4 carbon atoms. The alkoxy groups according to the inventionmay be substituted by one or more identical or different radicals.

According to the invention, “haloalkoxy” represents halogen-substitutedstraight-chain or branched O-alkyl preferably having 1 to 6 carbon atomssuch as, inter alia, difluoromethoxy, trifluoromethoxy,2,2-difluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy and2-chloro-1,1,2-trifluoroethoxy. Preference is furthermore given tohaloalkoxy groups having 1 to 4 carbon atoms. The haloalkoxy groupsaccording to the invention may be substituted by one or more identicalor different radicals.

According to the invention, “alkylthio” represents a straight-chain orbranched S-alkyl preferably having 1 to 6 carbon atoms such as, forexample, methylthio, ethylthio, n-propylthio, isopropylthio,n-butylthio, isobutylthio, s-butylthio and t-butylthio. Preference isfurthermore given to alkylthio groups having 1 to 4 carbon atoms. Thealkylthio groups according to the invention may be substituted by one ormore identical or different radicals.

Examples of haloalkylthioalkyl groups, i.e. halogen-substitutedalkylthio groups, are inter alia difluoromethylthio,trifluoromethylthio, trichloromethylthio, chlorodifluoromethylthio,1-fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio,1,1,2,2-tetrafluoroethylthio, 2,2,2-trifluoroethylthio or2-chloro-1,1,2-trifluoroethylthio.

According to the invention, “alkylsulphinyl” represents straight-chainor branched alkylsulphinyl preferably having 1 to 6 carbon atoms suchas, for example, methylsulphinyl, ethylsulphinyl, n-propylsulphinyl,isopropylsulphinyl, n-butylsulphinyl, isobutylsulphinyl,s-butylsulphinyl and t-butylsulphinyl. Preference is furthermore givento alkylsulphinyl groups having 1 to 4 carbon atoms. The alkylsulphinylgroups according to the invention may be substituted by one or moreidentical or different radicals.

Examples of haloalkylsulphinyl groups, i.e. halogen-substitutedalkylsulphinyl groups, are inter alia difluoromethylsulphinyl,trifluoromethylsulphinyl, trichloromethylsulphinyl,chlorodifluoromethylsulphinyl, 1-fluoroethylsulphinyl,2-fluoroethylsulphinyl, 2,2-difluoroethylsulphinyl,1,1,2,2-tetrafluoroethylsulphinyl, 2,2,2-trifluoroethylsulphinyl and2-chloro-1,1,2-trifluoroethylsulphinyl.

According to the invention, “alkylsulphonyl” represents straight-chainor branched alkylsulphonyl preferably having 1 to 6 carbon atoms suchas, for example, methylsulphonyl, ethylsulphonyl, n-propylsulphonyl,isopropylsulphonyl, n-butylsulphonyl, isobutylsulphonyl,s-butylsulphonyl and t-butylsulphonyl. Preference is furthermore givento alkylsulphonyl groups having 1 to 4 carbon atoms. The alkylsulphonylgroups according to the invention may be substituted by one or moreidentical or different radicals.

Examples of haloalkylsulphonyl groups, i.e. halogen-substitutedalkylsulphonyl groups, are inter alia difluoromethylsulphonyl,trifluoromethylsulphonyl, trichloromethylsulphonyl,chlorodifluoromethylsulphonyl, 1-fluoroethylsulphonyl,2-fluoroethylsulphonyl, 2,2-difluoroethylsulphonyl,1,1,2,2-tetrafluoroethylsulphonyl, 2,2,2-trifluoroethylsulphonyl and2-chloro-1,1,2-trifluoroethylsulphonyl.

According to the invention, “alkylcarbonyl” represents straight-chain orbranched alkyl-C(═O) preferably having 2 to 7 carbon atoms such asmethylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl,s-butylcarbonyl and t-butylcarbonyl. Preference is furthermore given toalkylcarbonyl groups having 1 to 4 carbon atoms. The alkylcarbonylgroups according to the invention may be substituted by one or moreidentical or different radicals.

According to the invention, “cycloalkylcarbonyl” representsstraight-chain or branched cyclooalkylcarbonyl preferably having 3 to 10carbon atoms in the cycloalkyl moiety such as, for example,cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl,cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl,bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octylcarbonyl and adamantylcarbonyl.Preference is furthermore given to cycloalkylcarbonyl having 3, 5 or 7carbon atoms in the cycloalkyl moiety. The cycloalkylcarbonyl groupsaccording to the invention may be substituted by one or more identicalor different radicals.

According to the invention, “alkoxycarbonyl”—alone or as a constituentof a chemical group—represents straight-chain or branchedalkoxycarbonyl, preferably having 1 to 6 carbon atoms or having 1 to 4carbon atoms in the alkoxy moiety such as, for example, methoxycarbonyl,ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, s-butoxycarbonyland t-butoxycarbonyl. The alkoxycarbonyl groups according to theinvention may be substituted by one or more identical or differentradicals.

According to the invention, “alkylaminocarbonyl” representsstraight-chain or branched alkylaminocarbonyl having preferably 1 to 6carbon atoms or 1 to 4 carbon atoms in the alkyl moiety, such as, forexample, methylaminocarbonyl, ethylaminocarbonyl, n-proylaminocarbonyl,isopropylaminocarbonyl, s-butylaminocarbonyl and t-butylaminocarbonyl.The alkylaminocarbonyl groups according to the invention may besubstituted by one or more identical or different radicals.

According to the invention, “N,N-dialkylaminocarbonyl” representsstraight-chain or branched N,N-dialkylaminocarbonyl having preferably 1to 6 carbon atoms or 1 to 4 carbon atoms in the alkyl moiety, such as,for example, N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl,N,N-di(n-propylamino)carbonyl, N,N-di(isopropylamino)carbonyl andN,N-di-(s-butylamino)carbonyl. The N,N-dialkyaminocarbonyl groupsaccording to the invention may be substituted by one or more identicalor different radicals.

According to the invention, “aryl” represents a mono-, bi- or polycyclicaromatic system having preferably 6 to 14, in particular 6 to 10 ringcarbon atoms such as, for example, phenyl, naphthyl, anthryl,phenanthrenyl, preferably phenyl. Furthermore, aryl also representspolycyclic systems such as tetrahydronaphtyl, indenyl, indanyl,fluorenyl, biphenylyl, where the bonding site is on the aromatic system.The aryl groups according to the invention may be substituted by one ormore identical or different radicals.

Examples for substituted aryls are the arylalkyl groups which maylikewise be substituted by one or more identical or different radicalsin the alkyl and/or aryl moiety. Examples for such arylalkyl groups areinter alia benzyl and 1-phenylethyl.

According to the invention, “heterocycle”, “heterocyclic ring” or“heterocyclic ring system” represents a carbocyclic ring system havingat least one ring in which at least one carbon atom is replaced by aheteroatom, preferably by a heteroatom from the group consisting of N,O, S, P, B, Si, Se, and which is saturated, unsaturated orheteroaromatic and may be unsubstituted or substituted by a substituentZ, where the point of attachment is located at a ring atom. Unlessdefined differently, the heterocyclic ring contains preferably 3 to 9ring atoms, especially 3 to 6 ring atoms, and one or more, preferably 1to 4, in particular 1, 2 or 3, heteroatoms in the heterocyclic ring,preferably from the group consisting of N, O, and S, although no twooxygen atoms should be directly adjacent. The heterocyclic rings usuallycontain not more than 4 nitrogen atoms and/or not more than 2 oxygenatoms and/or not more than 2 sulphur atoms. If the heterocyclyl radicalor the heterocyclic ring is optionally substituted, it can be fused toother carbocyclic or heterocyclic rings. In the case of optionallysubstituted heterocyclyl, the invention also embraces polycyclic systemssuch as, for example, 8-azabicyclo[3.2.1]octanyl or1-azabicyclo[2.2.1]heptyl. In the case of optionally substitutedheterocyclyl, the invention also embraces spirocyclic systems such as,for example, 1-oxa-5-azaspiro[2.3]hexyl.

Heterocyclyl groups according to the invention are, for example,piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dihydropyranyl,tetrahydropyranyl, dioxanyl, pyrrolinyl, pyrrolidinyl, imidazolinyl,imidazolidinyl, thiazolidinyl, oxazolidinyl, dioxolanyl, dioxolyl,pyrazolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxetanyl, oxiranyl,azetidinyl, aziridinyl, oxazetidinyl, oxaziridinyl, oxazepanyl,oxazinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrolidinyl,oxomorpholinyl, oxopiperazinyl and oxepanyl.

Heteroarylene, i.e. heteroaromatic systems, have a particular meaning.According to the invention, the term heteroaryl representsheteroaromatic compounds, i.e. completely unsaturated aromaticheterocyclic compounds which fall under the above definition ofheterocycles. Preference is given to 5- to 7-membered rings having 1 to3, preferably 1 or 2, identical or different heteroatoms from the groupabove. Heteroaryl groups according to the invention are, for example,furyl, thienyl, pyrazolyl, imidazolyl, 1,2,3- and 1,2,4-triazolyl,isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-, 1,3,4-, 1,2,4- and1,2,5-oxadiazolyl, azepinyl, pyrrolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, 1,3,5-, 1,2,4- and 1,2,3-triazinyl, 1,2,4-,1,3,2-, 1,3,6- and 1,2,6-oxazinyl, oxepinyl, thiepinyl,1,2,4-triazolonyl and 1,2,4-diazepinyl. The heteroaryl groups accordingto the invention may also be substituted by one or more identical ordifferent radicals.

Substituted groups such as a substituted alkyl, alkenyl, alkynyl,cycloalkyl, aryl, phenyl, benzyl, heterocyclyl and heteroaryl radicalare, for example, a substituted radical derived from the unsubstitutedbase structure, where the substituents are, for example, one or more,preferably 1, 2 or 3, radicals from the group of halogen, alkoxy,alkylthio, hydroxyl, amino, nitro, carboxyl or a group equivalent to thecarboxyl group, cyano, isocyano, azido, alkoxycarbonyl, alkylcarbonyl,formyl, carbamoyl, mono- and N,N-dialkylaminocarbonyl, substituted aminosuch as acylamino, mono- and N,N-dialkylamino, trialkylsilyl andoptionally substituted cycloalkyl, optionally substituted aryl,optionally substituted heterocyclyl, where each of the latter cyclicgroups may also be bonded via heteroatoms or divalent functional groupsas in the alkyl radicals mentioned, and alkylsulphinyl, including bothenantiomers of the alkylsulphonyl group, alkylsulphonyl,alkylphosphinyl, alkylphosphonyl and, in the case of cyclic radicals(=“cyclic skeleton”), also alkyl, haloalkyl, alkylthioalkyl,alkoxyalkyl, optionally substituted mono- and N,N-dialkylaminoalkyl andhydroxyalkyl.

The term “substituted groups”, such as substituted alkyl etc., includes,as substituents, in addition to the saturated hydrocarbonaceous radicalsmentioned, corresponding unsaturated aliphatic and aromatic radicalssuch as optionally substituted alkenyl, alkynyl, alkenyloxy, alkynyloxy,alkenylthio, alkynylthio, alkenyloxycarbonyl, alkynyloxycarbonyl,alkenylcarbonyl, alkynylcarbonyl, mono- and N,N-dialkenylaminocarbonyl,mono- and dialkynylaminocarbonyl, mono- and N,N-dialkenylamino, mono-and N,N-dialkynylamino, trialkenylsilyl, trialkynylsilyl, optionallysubstituted cycloalkenyl, optionally substituted cycloalkynyl, phenyl,phenoxy etc. In the case of substituted cyclic radicals with aliphaticcomponents in the ring, cyclic systems with those substituents bonded tothe ring by a double bond are also included, for example those having analkylidene group such as methylidene or ethylidene, or an oxo group,imino group or substituted imino group.

When two or more radicals form one or more rings, these may becarbocyclic, heterocyclic, saturated, partly saturated, unsaturated, forexample also aromatic and further substituted.

The substituents mentioned by way of example (“first substituent level”)may, if they contain hydrocarbon-containing moieties, optionally befurther substituted therein (“second substituent level”), for example byone of the substituents as defined for the first substituent level.Corresponding further substituent levels are possible. The term“substituted radical” preferably embraces just one or two substituentlevels.

Preferred substituents for the substituent levels are, for example,

amino, hydroxy, halogen, nitro, cyano, isocyano, mercapto,isothiocyanato, carboxyl, carboxamide, SF₅, aminosulphonyl, alkyl,cycloalkyl, alkenyl, cycloalkenyl, alkynyl, N-monoalkylamino,N,N-dialkylamino, N-alkanoylamino, alkoxy, alkenyloxy, alkynyloxy,cycloalkoxy, cycloalkenyloxy, alkoxycarbonyl, alkenyloxycarbonyl,alkynyloxycarbonyl, aryloxycarbonyl, alkanoyl, alkenylcarbonyl,alkynylcarbonyl, arylcarbonyl, alkylthio, cycloalkylthio, alkenylthio,cycloalkenylthio, alkynylthio, alkylsulphenyl and alkylsulphinyl, whereboth enantiomers of the alkylsulphinyl group are included,alkylsulphonyl, N-monoalkylaminosulphonyl, N,N-dialkylaminosulphonyl,alkylphosphinyl, alkylphosphonyl, where in the case of alkylphosphinyland alkylphosphonyl both enantiomers are included, N-alkylaminocarbonyl,N,N-dialkylaminocarbonyl, N-alkanoylaminocarbonyl,N-alkanoyl-N-alkylaminocarbonyl, aryl, aryloxy, benzyl, benzyloxy,benzylthio, arylthio, arylamino, benzylamino, heterocyclyl andtrialkylsilyl.

Substituents composed of a plurality of substituent levels arepreferably alkoxyalkyl, alkylthioalkyl, alkylthioalkoxy, alkoxyalkoxy,phenethyl, benzyloxy, haloalkyl, halocycloalkyl, haloalkoxy,haloalkylthio, haloalkylsulphinyl, haloalkylsulphonyl, haloalkanoyl,haloalkylcarbonyl, haloalkoxycarbonyl, haloalkoxyalkoxy,haloalkoxyalkylthio, haloalkoxyalkanoyl, haloalkoxyalkyl.

In the case of radicals having carbon atoms, preference is given tothose having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms,especially 1 or 2 carbon atoms. Preference is generally given tosubstituents from the group of halogen, e.g. fluorine and chlorine,(C₁-C₄)-alkyl, preferably methyl or ethyl, (C₁-C₄)-haloalkyl, preferablytrifluoromethyl, (C₁-C₄)-alkoxy, preferably methoxy or ethoxy,(C₁-C₄)-haloalkoxy, nitro and cyano. Particular preference is given hereto the substituents methyl, methoxy, fluorine and chlorine.

Substituted amino such as mono- or disubstituted amino means a radicalfrom the group of the substituted amino radicals which areN-substituted, for example, by one or two identical or differentradicals from the group consisting of alkyl, hydroxy, amino, alkoxy,acyl and aryl; preferably N-mono- and N,N-dialkylamino, (for examplemethylamino, ethylamino, N,N-dimethylamino, N,N-diethylamino,N,N-di-n-propylamino, N,N-diisopropylamino or N,N-dibutylamino), N-mono-or N,N-dialkoxyalkylamino groups (for example N-methoxymethylamino,N-methoxyethylamino, N,N-di(methoxymethyl)amino orN,N-di(methoxyethyl)amino), N-mono- and N,N-diarylamino, such asoptionally substituted anilines, acylamino, N,N-diacylamino,N-alkyl-N-arylamino, N-alkyl-N-acylamino and also saturatedN-heterocycles; preference is given here to alkyl radicals having 1 to 4carbon atoms; here, aryl is preferably phenyl or substituted phenyl; foracyl, the definition given further below applies, preferably(C₁-C₄)-alkanoyl. The same applies to substituted hydroxylamino orhydrazino.

According to the invention, the term “cyclic amino groups” embracesheteroaromatic or aliphatic ring systems having one or more nitrogenatoms. The heterocycles are saturated or unsaturated, consist of one ormore optionally fused ring systems and optionally contain furtherheteroatoms such as, for example, one or two nitrogen, oxygen and/orsulphur atoms. Furthermore, the term also includes groups having a spiroring or a bridged ring system. The number of atoms which form the cyclicamino groups is not limited, in the case of a one-ring system, forexample, the groups can consist of 3 to 8 ring atoms, and in the case ofa two-ring system of 7 to 11 atoms.

Examples of cyclic amino groups having saturated and unsaturatedmonocyclic groups having a nitrogen atom as heteroatom which may bementioned are 1-azetidinyl, pyrrolidino, 2-pyrrolidin-1-yl, 1-pyrrolyl,piperidino, 1,4-dihydropyrazin-1-yl, 1,2,5,6-tetrahydropyrazin-1-yl,1,4-dihydropyridin-1-yl, 1,2,5,6-tetrahydropyridin-1-yl,homopiperidinyl; examples of cyclic amino groups having saturated andunsaturated monocyclic groups having two or more nitrogen atoms asheteroatoms which may be mentioned are 1-imidazolidinyl, 1-imidazolyl,1-pyrazolyl, 1-triazolyl, 1-tetrazolyl, 1-piperazinyl,1-homopiperazinyl, 1,2-dihydropiperazin-1-yl, 1,2-dihydropyrimidin-1-yl,perhydropyrimidin-1-yl, 1,4-diazacycloheptan-1-yl; examples of cyclicamino groups having saturated and unsaturated monocyclic groups havingone or two oxygen atoms and one to three nitrogen atoms as heteroatoms,such as, for example, oxazolidin-3-yl, 2,3-dihydroisoxazol-2-yl,isoxazol-2-yl, 1,2,3-oxadiazin-2-yl, morpholino, examples of cyclicamino groups having saturated and unsaturated monocyclic groups havingone to three nitrogen atoms and one to two sulphur atoms as heteroatomswhich may be mentioned are thiazolidin-3-yl, isothiazolin-2-yl,thiomorpholino, or dioxothiomorpholino; examples of cyclic amino groupshaving saturated and unsaturated fused cyclic groups which may bementioned are indol-1-yl, 1,2-dihydrobenzimidazol-1-yl, perhydropyrrolopyrazin-2-yl; examples of cyclic amino groups having spirocyclic groupswhich may be mentioned are 2-azaspiro[4,5]decan-2-yl; examples of cyclicamino groups having bridged heterocyclic groups which may be mentionedare 2-azabicyclo[2.2.1]heptan-7-yl.

Substituted amino also includes quaternary ammonium compounds (salts)with four organic substituents on the nitrogen atom.

Optionally substituted phenyl is preferably phenyl which isunsubstituted or mono- or polysubstituted, preferably up totrisubstituted, by identical or different radicals from the group ofhalogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy, (C₁-C₄)-alkoxy-(C₁-C₄)-alkoxy,(C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, (C₁-C₄)-haloalkyl, (C₁-C₄)-haloalkoxy,(C₁-C₄)-alkylthio, (C₁-C₄)-haloalkylthio, cyano, isocyano and nitro, forexample o-, m- and p-tolyl, dimethylphenyls, 2-, 3- and 4-chlorophenyl,2-, 3- and 4-fluorophenyl, 2-, 3- and 4-trifluoromethyl- and-trichloromethylphenyl, 2,4-, 3,5-, 2,5- and 2,3-dichlorophenyl, o-, m-and p-methoxyphenyl.

Optionally substituted cycloalkyl is preferably cycloalkyl, which isunsubstituted or mono- or polysubstituted, preferably up totrisubstituted, by identical or different radicals from the group ofhalogen, cyano, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy,(C₁-C₄)-alkoxy-(C₁-C₄)-alkoxy, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl and (C₁-C₄)-haloalkoxy, especially by one or two(C₁-C₄)-alkyl radicals.

Optionally substituted heterocyclyl is preferably heterocyclyl which isunsubstituted or mono- or polysubstituted, preferably up totrisubstituted, by identical or different radicals from the group ofhalogen, cyano, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy,(C₁-C₄)-alkoxy-(C₁-C₄)-alkoxy, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-haloalkoxy, nitro and oxo, especially mono-or polysubstituted by radicals from the group of halogen, (C₁-C₄)-alkyl,(C₁-C₄)-alkoxy, (C₁-C₄)-haloalkyl and oxo, most preferably substitutedby one or two (C₁-C₄)-alkyl radicals.

Examples of alkyl-substituted heteroaryl groups are furylmethyl,thienylmethyl, pyrazolylmethyl, imidazolylmethyl, 1,2,3- and1,2,4-triazolylmethyl, isoxazolylmethyl, thiazolylmethyl,isothiazolylmethyl, 1,2,3-, 1,3,4-, 1,2,4- and 1,2,5-oxadiazolylmethyl,azepinylmethyl, pyrrolylmethyl, pyridylmethyl, pyridazinylmethyl,pyrimidinylmethyl, pyrazinylmethyl, 1,3,5-, 1,2,4- and1,2,3-triazinylmethyl, 1,2,4-, 1,3,2-, 1,3,6- and 1,2,6-oxazinylmethyl,oxepinylmethyl, thiepinylmethyl and 1,2,4-diazepinylmethyl.

Salts which are suitable according to the invention of the compoundsaccording to the invention, for example salts with bases or acidaddition salts, are all customary non-toxic salts, preferablyagriculturally and/or physiologically acceptable salts. For examplesalts with bases or acid addition salts. Preference is given to saltswith inorganic bases such as, for example, alkali metal salts (e.g.sodium, potassium or caesium salts), alkaline earth metal salts (e.g.calcium or magnesium salts), ammonium salts or salts with organic bases,in particular with organic amines, such as, for example,triethylammonium, dicyclohexylammonium, N,N′-dibenzylethylenediammonium,pyridinium, picolinium or ethanolammonium salts, salts with inorganicacids (e.g. hydrochlorides, hydrobromides, dihydrosulphates,trihydrosulphates or phosphates), salts with organic carboxylic acids ororganic sulphoacids (e.g. formates, acetates, trifluoroacetates,maleates, tartrates, methanesulphonates, benzenesulphonates or4-toluenesulphonates). It is known that t-amines such as some of thecompounds according to the invention are capable of forming N-oxides,which also represent salts according to the invention.

The compounds according to the invention may, depending on the nature ofthe substituents, be in the form of geometric and/or optically activeisomers or corresponding isomer mixtures in different compositions.These stereoisomers are, for example, enantiomers, diastereomers,atropisomers or geometric isomers. Accordingly, the inventionencompasses pure stereoisomers and any mixture of these isomers.

If appropriate, the compounds according to the invention may be presentin various polymorphic forms or as mixtures of different polymorphicforms. Both the pure polymorphs and the polymorph mixtures are providedby the invention and can be used according to the invention.

The compounds of the general formula (I) can be mixed or applied jointlywith other insecticidal, nematicidal, acaricidal or antimicrobial activecompounds. In these mixtures or joint applications, synergistic effectsoccur, i.e. the observed effect of these mixture or joint applicationsis higher than the total of the effects of the individual activecompounds in these applications. Examples of such mixing or combinationpartners are:

(1) Acetylcholinesterase (AChE) inhibitors, for example

carbamates, for example alanycarb (II-1-1), aldicarb (II-1-2),bendiocarb (II-1-3), benfuracarb (II-1-4), butocarboxim (II-1-5),butoxycarboxim (II-1-6), carbaryl (II-1-7), carbofuran (II-1-8),carbosulfan (II-1-9), ethiofencarb (II-1-10), fenobucarb (II-1-11),formetanate (II-1-12), furathiocarb (II-1-13), isoprocarb (II-1-14),methiocarb (II-1-15), methomyl (II-1-16), metolcarb (II-1-17), oxamyl(II-1-18), pirimicarb (II-1-19), propoxur (II-1-20), thiodicarb(II-1-21), thiofanox (II-1-22), triazamate (II-1-23), trimethacarb(II-1-24), XMC (II-1-25) and xylylcarb (II-1-26); ororganophosphates, for example acephate (II-1-27), azamethiphos(II-1-28), azinphos-ethyl (II-1-29), azinphos-methyl (II-1-30),cadusafos (II-1-31), chlorethoxyfos (II-1-32), chlorfenvinphos(II-1-33), chlormephos (II-1-34), chlorpyrifos (II-1-35),chlorpyrifos-methyl (II-1-36), coumaphos (II-1-37), cyanophos (II-1-38),demeton-S-methyl (II-1-39), diazinon (II-1-40), dichlorvos/DDVP(II-1-41), dicrotophos (II-1-42), dimethoate (II-1-43), dimethylvinphos(II-1-44), disulfoton (II-1-45), EPN (II-1-46), ethion (II-1-47),ethoprophos (II-1-48), famphur (II-1-49), fenamiphos (II-1-50),fenitrothion (II-1-51), fenthion (II-1-52), fosthiazate (II-1-53),heptenophos (II-1-54), imicyafos (II-1-55), isofenphos (II-1-56),isopropyl O-(methoxyaminothiophosphoryl) salicylate (II-1-57),isoxathion (II-1-58), malathion (II-1-59), mecarbam (II-1-60),methamidophos (II-1-61), methidathion (II-1-62), mevinphos (II-1-63),monocrotophos (II-1-64), naled (II-1-65), omethoate (II-1-66),oxydemeton-methyl (II-1-67), parathion (II-1-68), parathion-methyl(II-1-69), phenthoate (II-1-70), phorate (II-1-71), phosalone (II-1-72),phosmet (II-1-73), phosphamidon (II-1-74), phoxim (II-1-75),pirimiphos-methyl (II-1-76), profenofos (II-1-77), propetamphos(II-1-78), prothiofios (II-1-79), pyraclofos (II-1-80), pyridaphenthion(II-1-81), quinalphos (II-1-82), sulfotep (II-1-83), tebupirimfos(II-1-84), temephos (II-1-85), terbufos (II-1-86), tetrachlorvinphos(II-1-87), thiometon (II-1-88), triazophos (II-1-89), triclorfon(II-1-90) and vamidothion (II-1-91).

(2) GABA-gated chloride channel antagonists such as, for example,

cyclodiene organochlorins, for example chlordane (II-2-1) and endosulfan(II-2-2); orphenylpyrazoles (fiproles), for example ethiprole (II-2-3) and fipronil(II-2-4).

(3) Sodium channel modulators/voltage-dependent sodium channel blockerssuch as, for example,

pyrethroids, for example acrinathrin (II-3-1), allethrin (II-3-2),d-cis-trans allethrin (II-3-3), d-trans allethrin (II-3-4), bifenthrin(II-3-5), bioallethrin (II-3-6), bioallethrin S-cyclopentenyl isomer(II-3-7), bioresmethrin (II-3-8), cycloprothrin (II-3-9), cyfluthrin(II-3-10), beta-cyfluthrin (II-3-11), cyhalothrin (II-3-12),lambda-cyhalothrin (II-3-13), gamma-cyhalothrin (II-3-14), cypermethrin(II-3-15), alpha-cypermethrin (II-3-16), beta-cypermethrin (II-3-17),theta-cypermethrin (II-3-18), zeta-cypermethrin (II-3-19), cyphenothrin[(1R)-trans isomers] (II-3-20), deltamethrin (II-3-21), empenthrin[(EZ)-(1R) isomers] (II-3-22), esfenvalerate (II-3-23), etofenprox(II-3-24), fenpropathrin (II-3-25), fenvalerate (II-3-26), flucythrinate(II-3-27), flumethrin (II-3-28), tau-fluvalinate (II-3-29), halfenprox(II-3-30), imiprothrin (II-3-31), kadethrin (II-3-32), permethrin(II-3-33), phenothrin [(1R)-trans isomer] (II-3-34), prallethrin(II-3-35), pyrethrine (pyrethrum) (II-3-36), resmethrin (II-3-37),silafluofen (II-3-38), tefluthrin (II-3-39), tetramethrin (II-3-40),tetramethrin [(1R) isomers)] (II-3-41), tralomethrin (II-3-42) andtransfluthrin (II-3-43); orDDT (II-3-44); or methoxychlor (II-3-45).

(4) Nicotinergic acetylcholine receptor (nAChR) agonists such as, forexample,

neonicotinoids, for example acetamiprid (II-4-1), clothianidin (II-4-2),dinotefuran (II-4-3), imidacloprid (II-4-4), nitenpyram (II-4-5),thiacloprid (II-4-6) and thiamethoxam (II-4-7); ornicotine (II-4-8).

(5) Nicotinergic acetylcholine receptor (nAChR) allosteric activatorssuch as, for example,

spinosyns, for example spinetoram (II-5-1) and spinosad (II-5-2).

(6) Chloride channel activators such as, for example,

avermectins/milbemycins, e.g. abamectin (II-6-1), emamectin benzoate(II-6-2), lepimectin (II-6-3) and milbemectin (II-6-4).

(7) Juvenile hormone imitators such as, for example,

juvenile hormone analogues, for example hydroprene (II-7-1), kinoprene(II-7-2) and methoprene (II-7-3); orfenoxycarb (II-7-4); or pyriproxyfen (II-7-5).

(8) Active compounds with unknown or nonspecific mechanisms of actionsuch as, for example

alkyl halides, e.g. methyl bromide (II-8-1) and other alkyl halides; orchloropicrin (II-8-2); or sulphuryl fluoride (II-8-3); or borax(II-8-4); or tartar emetic (II-8-5).

(9) Selective antifeedants, for example pymetrozine (II-9-1); orflonicamid (II-9-2).

(10) Mite growth inhibitors, for example clofentezine (II-10-1),hexythiazox (II-10-2) and diflovidazin (II-10-3); or

etoxazole (II-10-4).

(11) Microbial disruptors of the insect gut membrane, for exampleBacillus thuringiensis subspecies israelensis (II-11-1), Bacillussphaericus (II-11-2), Bacillus thuringiensis subspecies aizawai(II-11-3), Bacillus thuringiensis subspecies kurstaki (II-11-4),Bacillus thuringiensis subspecies tenebrionis (II-11-5) and BT plantproteins: Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab, mCry3A, Cry3Ab, Cry3Bb,Cry34/35Ab1 (II-11-6).

(12) Oxidative phosphorylation inhibitors, ATP disruptors such as, forexample, diafenthiuron (II-12-1); or organo tin compounds, e.g.azocyclotin (II-12-2), cyhexatin (II-12-3) and fenbutatin oxide(II-12-4); or propargite (II-12-5); or tetradifon (II-12-6).

(13) Oxidative phosphorylation decouplers acting by interrupting the Hproton gradient such as, for example, chlorfenapyr (II-13-1), DNOC(II-13-2) and sulfluramid (II-13-3).

(14) Nicotinergic acetylcholine receptor antagonists such as, forexample, bensultap (II-14-1), cartap hydrochloride (II-14-2), thiocyclam(II-14-3) and thiosultap-sodium (II-14-4).

(15) Chitin biosynthesis inhibitors, type 0, such as, for example,bistrifluoron (II-15-1), chlorfluazuron (II-15-2), diflubenzuron(II-15-3), flucycloxuron (II-15-4), flufenoxuron (II-15-5), hexaflumuron(II-15-6), lufenuron (II-15-7), novaluron (II-15-8), noviflumuron(II-15-9), teflubenzuron (II-15-10) and triflumuron (II-15-11).

(16) Chitin biosynthesis inhibitors, type 1, such as, for example,buprofezin (II-16-1).

(17) Moulting disruptors, dipteran such as, for example, cyromazine(II-17-1).

(18) Ecdysone receptor agonists such as, for example, chromafenozide(II-18-1), halofenozide (II-18-2), methoxyfenozide (II-18-3) andtebufenozide (II-18-4).

(19) Octopaminergic agonists such as, for example, amitraz (II-19-1).

(20) Complex-III electron transport inhibitors such as, for example,hydramethylnone (II-20-1); or acequinocyl (II-20-2); or fluacrypyrim(II-20-3).

(21) Complex-I electron transport inhibitors, for example

METI acaricides, for example fenazaquin (II-21-1), fenpyroximate(II-21-2), pyrimidifen (II-21-3), pyridaben (II-21-4), tebufenpyrad(II-21-5) and tolfenpyrad (II-21-6); orrotenone (Derris) (II-21-7).

(22) Voltage-dependent sodium channel blockers, for example indoxacarb(II-22-1); or metaflumizone (II-22-2).

(23) Inhibitors of acetyl-CoA carboxylase such as, for example,

tetronic and tetramic acid derivatives, for example spirodiclofen(II-23-1), spiromesifen (II-23-2) and spirotetramat (II-23-3).

(24) Complex-IV electron transport inhibitors such as, for example,

phosphines, for example aluminium phosphide (II-24-1), calcium phosphide(II-24-2), phosphine (II-24-3) and zinc phosphide (II-24-4); orcyanide (II-24-5).

(25) Complex-II electron transport inhibitors such as, for example,cyenopyrafen (II-25-1).

(28) Ryanodine receptor effectors such as, for example,

diamides, for example chlorantraniliprole (II-28-1) and flubendiamide(II-28-2).

Further active compounds with unknown mechanism of action such as, forexample, amidoflumet (II-29-1), azadirachtin (II-29-2), benclothiaz(II-29-3), benzoximate (II-29-4), bifenazate (II-29-5), bromopropylate(II-29-6), chinomethionat (II-29-7), cryolite (II-29-8),cyantraniliprole (Cyazypyr) (II-29-9), cyflumetofen (II-29-10), dicofol(II-29-11), diflovidazin (II-29-12), fluensulfone (II-29-13), flufenerim(II-29-14), flufiprole (II-29-15), fluopyram (II-29-16), fufenozide(II-29-17), imidaclothiz (II-29-18), iprodione (II-29-19), pyridalyl(II-29-20), pyrifluquinazon (II-29-21) and iodomethane (II-29-22);furthermore preparations based on Bacillus firmus (I-1582, BioNeem,Votivo) (II-29-23) and also the following known active compounds:

3-bromo-N-{2-bromo-4-chloro-6-[(1-cyclopropylethyl)carbamoyl]phenyl}-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide(II-29-24) (known from WO2005/077934),4-{[(6-bromopyrid-3-yl)methyl](2-fluoroethyl)amino}furan-2(5H)-one(II-29-25) (known from WO2007/115644),4-{[(6-fluoropyrid-3-yl)methyl](2,2-difluoroethyl)amino}furan-2(5H)-one(II-29-26) (known from WO2007/115644),4-{[(2-chloro-1,3-thiazol-5-yl)methyl](2-fluoroethyl)amino}furan-2(5H)-one(II-29-27) (known from WO2007/115644),4-{[(6-chloropyrid-3-yl)methyl](2-fluoroethyl)amino}furan-2(5H)-one(II-29-28) (known from WO2007/115644),4-{[(6-chloropyrid-3-yl)methyl](2,2-difluoroethyl)amino}furan-2(5H)-one(II-29-29) (known from WO2007/115644),4-{[(6-chloro-5-fluoropyrid-3-yl)methyl](methyl)amino}furan-2(5H)-one(II-29-30) (known from WO2007/115643),4-{[(5,6-dichloropyrid-3-yl)methyl](2-fluoroethyl)amino}furan-2(5H)-one(II-29-31) (known from WO2007/115646),4-{[(6-chloro-5-fluoropyrid-3-yl)methyl](cyclopropyl)amino}furan-2(5H)-one(II-29-32) (known from WO2007/115643),4-{[(6-chloropyrid-3-yl)methyl](cyclopropyl)amino}furan-2(5H)-one(II-29-33) (known from EP-A-0 539 588),4-{[(6-chloropyrid-3-yl)methyl](methyl)amino}furan-2(5H)-one (II-29-34)(known from EP-A-0 539 588),{[1-(6-chloropyridin-3-yl)ethyl](methyl)oxido-λ⁴-sulphanylidene}cyanamide(II-29-35) (known from WO2007/149134) and diastereomers thereof{[(1R)-1-(6-chloropyridin-3-yl)ethyl](methyl)oxido-λ⁴-sulphanylidene}cyanamide(A) (II-29-36) and{[(1S)-1-(6-chloropyridin-3-yl)ethyl]imethylloxido-λ⁴-sulphanylidene}cyanamide(B) (II-29-37) (likewise known from WO2007/149134) and sulfoxaflor(II-29-38) (also known from WO2007/149134) and diastereomers thereof[(R)-methyl(oxido){(1R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-λ⁴-sulphanylidene]cyanamide(A1) (II-29-39) and[(S)-methyl(oxido){(1S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-λ⁴-sulphanylidene]cyanamide(A2) (II-29-40), designated as diastereomer group A (known from WO2010/074747, WO 2010/074751),[(R)-methyl(oxido){(1S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-λ⁴-sulphanylidene]cyanamide(B1) (II-29-41) and [(S)-methyl(oxido){(1R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-λ⁴-sulphanylidene]cyanamide(B2) (II-29-42), designated as diastereomer group B (likewise known fromWO 2010/074747, WO 2010/074751) and11-(4-chloro-2,6-dimethylphenyl)-12-hydroxy-1,4-dioxa-9-azadispiro[4.2.4.2]tetradec-11-en-10-one(II-29-43) (known from WO2006/089633),3-(4′-fluoro-2,4-dimethylbiphenyl-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4.5]dec-3-en-2-one(II-29-44) (known from WO2008/067911),1-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)sulphinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazol-5-amine(II-29-45) (known from WO2006/043635),[(3S,4aR,12R,12aS,12bS)-3-[(cyclopropylcarbonyl)oxy]-6,12-dihydroxy-4,12b-dimethyl-11-oxo-9-(pyridin-3-yl)-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromen-4-yl]methylcyclopropanecarboxylate (II-29-46) (known from WO2008/066153),2-cyano-3-(difluoromethoxy)-N,N-dimethylbenzenesulphonamide (II-29-47)(known from WO2006/056433),2-cyano-3-(difluoromethoxy)-N-methylbenzenesulphonamide (II-29-48)(known from WO2006/100288),2-cyano-3-(difluoromethoxy)-N-ethylbenzenesulphonamide (II-29-49) (knownfrom WO2005/035486),4-(difluoromethoxy)-N-ethyl-N-methyl-1,2-benzothiazol-3-amine1,1-dioxide (II-29-50) (known from WO2007/057407),N-[1-(2,3-dimethylphenyl)-2-(3,5-dimethylphenyl)ethyl]-4,5-dihydro-1,3-thiazol-2-amine(II-29-51) (known from WO2008/104503),{1′-[(2E)-3-(4-chlorophenyl)prop-2-en-1-yl]-5-fluorospiro[indole-3,4′-piperidin]-1(2H)-yl}(2-chloropyridin-4-yl)methanone(II-29-52) (known from WO2003/106457),3-(2,5-dimethylphenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one(II-29-53) (known from WO2009/049851),3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-ylethyl carbonate (II-29-54) (known from WO2009/049851),4-(but-2-yn-1-yloxy)-6-(3,5-dimethylpiperidin-1-yl)-5-fluoropyrimidine(II-29-55) (known from WO2004/099160),(2,2,3,3,4,4,5,5-octafluoropentyl)(3,3,3-trifluoropropyl)malononitrile(II-29-56) (known from WO2005/063094),(2,2,3,3,4,4,5,5-octafluoropentyl)(3,3,4,4,4-pentafluorobutyl)malononitrile(II-29-57) (known from WO2005/063094),8-[2-(cyclopropylmethoxy)-4-(trifluoromethyl)phenoxy]-3-[6-(trifluoromethyl)pyridazin-3-yl]-3-azabicyclo[3.2.1]octane(II-29-58) (known from WO2007/040280),2-ethyl-7-methoxy-3-methyl-6-[(2,2,3,3-tetrafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)oxy]quinolin-4-ylmethylcarbonate (II-29-59) (known from JP2008/110953),2-ethyl-7-methoxy-3-methyl-6-[(2,2,3,3-tetrafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)oxy]quinolin-4-ylacetate (II-29-60) (known from JP2008/110953), PF1364 (CAS Reg. No.1204776-60-2) (II-29-61) (known from JP2010/018586),5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(1H-1,2,4-triazol-1-yl)benzonitrile(II-29-62) (known from WO2007/075459),5-[5-(2-chloropyridin-4-yl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(1H-1,2,4-triazol-1-yl)benzonitrile(II-29-63) (known from WO2007/075459),4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methyl-N-{2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}benzamide(II-29-64) (known from WO2005/085216),4-{[(6-chloropyridin-3-yl)methyl](cyclopropyl)amino}-1,3-oxazol-2(5H)-one(II-29-65), 4-{[(6-chloropyridin-3-yl)methyl](2,2-difluoroethyl)amino}-1,3-oxazol-2(5H)-one (II-29-66),4-{[(6-chloropyridin-3-yl)methyl] (ethyl)amino}-1,3-oxazol-2(5H)-one(II-29-67),4-{[(6-chloropyridin-3-yl)methyl](methyl)amino}-1,3-oxazol-2(5H)-one(II-29-68) (all known from WO2010/005692), NNI-0711 (II-29-69) (knownfrom WO2002/096882),1-acetyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-methoxypropan-2-yl)-3-isobutylphenyl]-N-isobutyryl-3,5-dimethyl-1H-pyrazole-4-carboxamide(II-29-70) (known from WO2002/096882), methyl2-[2-({[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]carbonyl}amino)-5-chloro-3-methylbenzoyl]-2-methylhydrazinecarboxylate(II-29-71) (known from WO2005/085216), methyl2-[2-({[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]carbonyl}amino)-5-cyano-3-methylbenzoyl]-2-ethylhydrazinecarboxylate(II-29-72) (known from WO2005/085216), methyl2-[2-({[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]carbonyl}amino)-5-cyano-3-methylbenzoyl]-2-methylhydrazinecarboxylate(II-29-73) (known from WO2005/085216), methyl2-[3,5-dibromo-2-({[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]carbonyl}amino)benzoyl]-1,2-diethylhydrazinecarboxylate(II-29-74) (known from WO2005/085216), methyl2-[3,5-dibromo-2-({[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]carbonyl}amino)benzoyl]-2-ethylhydrazinecarboxylate(II-29-75) (known from WO2005/085216),(5RS,7RS;5RS,7SR)-1-(6-chloro-3-pyridylmethyl)-1,2,3,5,6,7-hexahydro-7-methyl-8-nitro-5-propoxyimidazo[1,2-a]pyridine(II-29-76) (known from WO2007/101369),2-{6-[2-(5-fluoropyridin-3-yl)-1,3-thiazol-5-yl]pyridin-2-yl}pyrimidine(II-29-77) (known from WO2010/006713),2-{6-[2-(pyridin-3-yl)-1,3-thiazol-5-yl]pyridin-2-yl}pyrimidine(II-29-78) (known from WO2010/006713),1-(3-chloropyridin-2-yl)-N-[4-cyano-2-methyl-6-(methylcarbamoyl)phenyl]-3-{[5-(trifluoromethyl)-1H-tetrazol-1-yl]methyl}-1H-pyrazole-5-carboxamide(II-29-79) (known from WO2010/069502),1-(3-chloropyridin-2-yl)-N-[4-cyano-2-methyl-6-(methylcarbamoyl)phenyl]-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide(II-29-80) (known from WO2010/069502),N-[2-(tert-butylcarbamoyl)-4-cyano-6-methylphenyl]-1-(3-chloropyridin-2-yl)-3-{[5-(trifluoromethyl)-1H-tetrazol-1-yl]methyl}-1H-pyrazole-5-carboxamide(II-29-81) (known from WO2010/069502),N-[2-(tert-butylcarbamoyl)-4-cyano-6-methylphenyl]-1-(3-chloropyridin-2-yl)-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide(II-29-82) (known from WO2010/069502) and(1E)-N-[(6-chloropyridin-3-yl)methyl]-N′-cyano-N-(2,2-difluoroethyl)ethanimidamide(II-29-83) (known from WO2008/009360).

Antimicrobially active compounds:

(1) Ergosterol biosynthesis inhibitors, for example aldimorph,azaconazole, bitertanol, bromuconazole, cyproconazole, diclobutrazole,difenoconazole, diniconazole, diniconazole-M, dodemorph, dodemorphacetate, epoxiconazole, etaconazole, fenarimol, fenbuconazole,fenhexamid, fenpropidin, fenpropimorph, fluquinconazole, flurprimidol,flusilazole, flutriafol, furconazole, furconazole-cis, hexaconazole,imazalil, imazalil sulphate, imibenconazole, ipconazole, metconazole,myclobutanil, naftifin, nuarimol, oxpoconazole, paclobutrazole,pefurazoate, penconazole, piperalin, prochloraz, propiconazole,prothioconazole, pyributicarb, pyrifenox, quinconazole, simeconazole,spiroxamine, tebuconazole, terbinafine, tetraconazole, triadimefon,triadimenol, tridemorph, triflumizole, triforine, triticonazole,uniconazole, uniconazole-p, viniconazole, voriconazole,1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)cycloheptanol, methyl1-(2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)-1H-imidazole-5-carboxylate,N′-{5-(difluoromethyl)-2-methyl-4-[3-(trimethylsilyl)propoxy]phenyl}-N-ethyl-N-methylimidoformamide,N-ethyl-N-methyl-N′-{2-methyl-5-(trifluoromethyl)-4-[3-(trimethylsilyl)propoxy]phenyl}imidoformamideandO-[1-(4-methoxyphenoxy)-3,3-dimethylbutan-2-yl]-1H-imidazole-1-carbothioate.

(2) Respiration inhibitors (respiratory chain inhibitors), for examplebixafen, boscalid, carboxin, diflumetorim, fenfuram, fluopyram,flutolanil, fluxapyroxad, furametpyr, furmecyclox, isopyrazam mixture ofthe syn-epimeric racemate 1RS,4SR,9RS and of the anti-epimeric racemate1RS,4SR,9SR, isopyrazam (anti-epimeric racemate), isopyrazam(anti-epimeric enantiomer 1R,4S,9S), isopyrazam (anti-epimericenantiomer 1S,4R,9R), isopyrazam (syn-epimeric racemate 1RS,4SR,9RS),isopyrazam (syn-epimeric enantiomer 1R,4S,9R), isopyrazam (syn-epimericenantiomer 1S,4R,9S), mepronil, oxycarboxin, penflufen, penthiopyrad,sedaxane, thifluzamide,1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide,3-(difluoromethyl)-1-methyl-N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-1H-pyrazole-4-carboxamide,3-(difluoromethyl)-N-[4-fluoro-2-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-1-methyl-1H-pyrazole-4-carboxamideandN-[1-(2,4-dichlorophenyl)-1-methoxypropan-2-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide,

(3) Respiration inhibitors (respiratory chain inhibitors) acting oncomplex III of the respiratory chain, for example ametoctradin,amisulbrom, azoxystrobin, cyazofamid, dimoxystrobin, enestroburin,famoxadone, fenamidone, fluoxastrobin, kresoxim-methyl, metominostrobin,orysastrobin, picoxystrobin, pyraclostrobin, pyrametostrobin,pyraoxystrobin, pyribencarb, trifloxystrobin,(2E)-2-(2-{[6-(3-chloro-2-methylphenoxy)-5-fluoropyrimidin-4-yl]oxy}phenyl)-2-(methoxyimino)-N-methylethanamide,(2E)-2-(methoxyimino)-N-methyl-2-(2-{[({(1E)-1-[3-(trifluoromethyl)phenyl]ethylidene}amino)oxy]methyl}phenyl)ethanamide,(2E)-2-(methoxyimino)-N-methyl-2-{2-[(E)-({1-[3-(trifluoromethyl)phenyl]ethoxy}imino)methyl]phenyl}ethanamide,(2E)-2-{2-[({[(1E)-1-(3-{[(E)-1-fluoro-2-phenylethenyl]oxy}phenyl)ethylidene]amino}oxy)methyl]phenyl}-2-(methoxyimino)-N-methylethanamide,(2E)-2-{2-[({[(2E,3E)-4-(2,6-dichlorophenyl)but-3-en-2-ylidene]amino}oxy)methyl]phenyl}-2-(methoxyimino)-N-methylethanamide,2-chloro-N-(1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)pyridine-3-carboxamide,5-methoxy-2-methyl-4-(2-{[({(1E)-1-[3-(trifluoromethyl)phenyl]ethylidene}amino)oxy]methyl}phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one,methyl(2E)-2-{2-[({cyclopropyl[(4-methoxyphenyl)imino]methyl}sulphanyl)methyl]phenyl}-3-methoxyprop-2-enoate,N-(3-ethyl-3,5,5-trimethylcyclohexyl)-3-(formylamino)-2-hydroxybenzamide,2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamideand(2R)-2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamide.

(4) Mitosis and cell division inhibitors, for example benomyl,carbendazim, chlorfenazole, diethofencarb, ethaboxam, fluopicolide,fuberidazole, pencycuron, thiabendazole, thiophanate-methyl,thiophanate, zoxamide,5-chloro-7-(4-methylpiperidin-1-yl)-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidineand3-chloro-5-(6-chloropyridin-3-yl)-6-methyl-4-(2,4,6-trifluorophenyl)pyridazine.

(5) Compounds with multisite activity, for example Bordeaux mixture,captafol, captan, chlorothalonil, copper preparations such as copperhydroxide, copper naphthenate, copper oxide, copper oxychloride, coppersulphate, dichlofluanid, dithianon, dodine, dodine free base, ferbam,fluorofolpet, folpet, guazatine, guazatine acetate, iminoctadine,iminoctadine albesilate, iminoctadine triacetate, mancopper, mancozeb,maneb, metiram, metiram zinc, oxine-copper, propamidine, propineb,sulphur and sulphur preparations, for example calcium polysulphide,thiram, tolylfluanid, zineb and ziram.

(6) Resistance inductors, for example acibenzolar-5-methyl, isotianil,probenazole and tiadinil.

(7) Amino acid and protein biosynthesis inhibitors, for exampleandoprim, blasticidin-S, cyprodinil, kasugamycin, kasugamycinhydrochloride hydrate, mepanipyrim and pyrimethanil,

(8) ATP production inhibitors, for example fentin acetate, fentinchloride, fentin hydroxide and silthiofam.

(9) Cell wall synthesis inhibitors, for example benthiavalicarb,dimethomorph, flumorph, iprovalicarb, mandipropamid, polyoxins,polyoxorim, validamycin A and valifenalate.

(10) Lipid and membrane synthesis inhibitors, for example biphenyl,chloroneb, dicloran, edifenphos, etridiazole, iodocarb, iprobenfos,isoprothiolane, propamocarb, propamocarb hydrochloride, prothiocarb,pyrazophos, quintozene, tecnazene and tolclofos-methyl.

(11) Melanin biosynthesis inhibitors, for example carpropamid,diclocymet, fenoxanil, phthalide, pyroquilon and tricyclazole.

(12) Nucleic acid synthesis inhibitors, for example benalaxyl,benalaxyl-M (kiralaxyl), bupirimate, clozylacon, dimethirimol,ethirimol, furalaxyl, hymexazol, metalaxyl, metalaxyl-M (mefenoxam),ofurace, oxadixyl, oxolinic acid,

(13) Signal transduction inhibitors, for example chlozolinate,fenpiclonil, fludioxonil, iprodione, procymidone, quinoxyfen andvinclozolin.

(14) Decouplers, for example binapacryl, dinocap, ferimzone, fluazinamand meptyldinocap.

(15) Further compounds, for example benthiazole, bethoxazin, capsimycin,carvone, chinomethionat, chlazafenone, cufraneb, cyflufenamid,cymoxanil, cyprosulfamide, dazomet, debacarb, dichlorophen, diclomezine,difenzoquat, difenzoquat methylsulphate, diphenylamine, ecomat,fenpyrazamine, flumetover, fluoromide, flusulfamide, flutianil,fosetyl-aluminium, fosetyl-calcium, fosetyl-sodium, hexachlorobenzene,irumamycin, methasulfocarb, methyl isothiocyanate, metrafenon,mildiomycin, natamycin, nickel dimethyldithiocarbamate,nitrothal-isopropyl, octhilinone, oxamocarb, oxyfenthiin,pentachlorophenol and salts thereof, phenothrin, phosphoric acid andsalts thereof, propamocarb-fosetylate, propanosine-sodium, proquinazid,pyrroInitrin, tebufloquin, tecloftalam, tolnifanid, triazoxide,trichlamide, zarilamide,1-(4-{4-[(5R)-5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone,1-(4-{4-[(5S)-5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone,1-(4-{4-[5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone,1-(4-methoxyphenoxy)-3,3-dimethylbutan-2-yl 1H-imidazole-1-carboxylate,2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine,2,3-dibutyl-6-chlorothieno[2,3-d]pyrimidin-4(3H)-one,2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[(5R)-5-phenyl-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone,2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[(5S)-5-phenyl-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone,2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1-{4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidin-1-yl}ethanone,2-butoxy-6-iodo-3-propyl-4H-chromen-4-one,2-chloro-5-[2-chloro-1-(2,6-difluoro-4-methoxyphenyl)-4-methyl-1H-imidazol-5-yl]pyridine,2-phenylphenol and salts thereof,3,4,5-trichloropyridine-2,6-dicarbonitrile,3-[5-(4-chlorophenyl)-2,3-dimethyl-1,2-oxazolidin-3-yl]pyridine,3-chloro-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-6-methylpyridazine,4-(4-chlorophenyl)-5-(2,6-difluorophenyl)-3,6-dimethylpyridazine,5-amino-1,3,4-thiadiazole-2-thiol,5-chloro-N′-phenyl-N′-(prop-2-yn-1-yl)thiophene-2-sulphonohydrazide,5-methyl-6-octyl[1,2,4]triazolo[1,5-a]pyrimidine-7-amine, ethyl(2Z)-3-amino-2-cyano-3-phenylprop-2-enoate,N-(4-chlorobenzyl)-3-[3-methoxy-4-(prop-2-yn-1-yloxy)phenyl]propanamide,N-[(4-chlorophenyl)(cyano)methyl]-3-[3-methoxy-4-(prop-2-yn-1-yloxy)phenyl]propanamide,N-[(5-bromo-3-chloropyridin-2-yl)methyl]-2,4-dichloropyridine-3-carboxamide,N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2,4-dichloropyridine-3-carboxamide,N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2-fluoro-4-iodopyridine-3-carboxamide,N-{(E)-[(cyclopropylmethoxy)imino][6-(difluoromethoxy)-2,3-difluorophenyl]methyl}-2-phenylacetamide,N-{(Z)-[(cyclopropylmethoxy)imino][6-(difluoromethoxy)-2,3-difluorophenyl]methyl}-2-phenylacetamide,N-methyl-2-(1-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1,3-thiazole-4-carboxamide,N-methyl-2-(1-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-1,3-thiazole-4-carboxamide,N-methyl-2-(1-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-1,3-thiazole-4-carboxamide,pentyl{6-[({[(1-methyl-1H-tetrazol-5-yl)(phenyl)methylidene]amino}oxy)methyl]pyridin-2-yl}carbamate,phenazine-1-carboxylic acid, quinolin-8-ol and quinolin-8-ol sulphate(2:1),

All mixing components mentioned in classes (1) to (15) can, if they arecapable on the basis of their functional groups, optionally form saltswith suitable bases or acids.

(16) Further compounds, for example1-methyl-3-(trifluoromethyl)-N-[2′-(trifluoromethyl)biphenyl-2-yl]-1H-pyrazole-4-carboxamide,N-(4′-chlorobiphenyl-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide,N-(2′,4′-dichlorobiphenyl-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide,3-(difluoromethyl)-1-methyl-N-[4′-(trifluoromethyl)biphenyl-2-yl]-1H-pyrazole-4-carboxamide,N-(2′,5′-difluorobiphenyl-2-yl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide,3-(difluoromethyl)-1-methyl-N-[4′-(prop-1-yn-1-yl)biphenyl-2-yl]-1H-pyrazole-4-carboxamide,5-fluoro-1,3-dimethyl-N-[4′-(prop-1-yn-1-yl)biphenyl-2-yl]-1H-pyrazole-4-carboxamide,2-chloro-N-[4′-(prop-1-yn-1-yl)biphenyl-2-yl]pyridine-3-carboxamide,3-(difluoromethyl)-N-[4′-(3,3-dimethylbut-1-yn-1-yl)biphenyl-2-yl]-1-methyl-1H-pyrazole-4-carboxamide,N-[4′-(3,3-dimethylbut-1-yn-1-yl)biphenyl-2-yl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide,3-(difluoromethyl)-N-(4′-ethynylbiphenyl-2-yl)-1-methyl-1H-pyrazole-4-carboxamide,N-(4′-ethynylbiphenyl-2-yl)-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide,2-chloro-N-(4′-ethynylbiphenyl-2-yl)pyridine-3-carboxamide,2-chloro-N-[4′-(3,3-dimethylbut-1-yn-1-yl)biphenyl-2-yl]pyridine-3-carboxamide,4-(difluoromethyl)-2-methyl-N-[4′-(trifluoromethyl)biphenyl-2-yl]-1,3-thiazole-5-carboxamide,5-fluoro-N-[4′-(3-hydroxy-3-methylbut-1-yn-1-yl)biphenyl-2-yl]-1,3-dimethyl-1H-pyrazole-4-carboxamide,2-chloro-N-[4′-(3-hydroxy-3-methylbut-1-yn-1-yl)biphenyl-2-yl]pyridine-3-carboxamide,3-(difluoromethyl)-N-[4′-(3-methoxy-3-methylbut-1-yn-1-yl)biphenyl-2-yl]-1-methyl-1H-pyrazole-4-carboxamide,5-fluoro-N-[4′-(3-methoxy-3-methylbut-1-yn-1-yl)biphenyl-2-yl]-1,3-dimethyl-1H-pyrazole-4-carboxamide,2-chloro-N-[4′-(3-methoxy-3-methylbut-1-yn-1-yl)biphenyl-2-yl]pyridine-3-carboxamide,(5-bromo-2-methoxy-4-methylpyridin-3-yl)(2,3,4-trimethoxy-6-methylphenyl)methanoneandN-[2-(4-{[3-(4-chlorophenyl)prop-2-yn-1-yl]oxy}-3-methoxyphenyl)ethyl]-N2-(methylsulphonyl)valinamide.

The active compounds identified here by their common names are known andare described, for example, in the pesticide handbook (“The PesticideManual” 14th Ed., British Crop Protection Council 2006) or can be foundon the Internet (e.g. http://www.alanwood.net/pesticides).

All mixing components mentioned in classes (1) to (16) can, if they arecapable on the basis of their functional groups, optionally form saltswith suitable bases or acids.

Finally, it has been found that the novel compounds of the formula (I),whilst being well tolerated by plants, with favourable homeothermtoxicity and good environmental compatibility, are suitable inparticular for controlling animal pests, especially arthropods, insects,arachnids, helminths, nematodes and molluscs, which are encountered inagriculture, in forests, in the protection of stored products andmaterials and in the hygiene sector, or in the animal health sector. Thecompounds according to the invention can likewise be used in the animalhealth sector, for example for controlling endo- and/or ectoparasites.

The compounds according to the invention can be used as agents forcontrolling animal pests, preferably as crop protection agents. They areeffective against normally sensitive and resistant species and againstall or some stages of development.

The compounds according to the invention can be converted into generallyknown formulations. In general, such formulations comprise from 0.01 to98% by weight of active compound, preferably from 0.5 to 90% by weight.

The compounds according to the invention can be present in theircommercially available formulations and in the use forms, prepared fromthese formulations, as a mixture with other active compounds orsynergists. Synergists are compounds which enhance the action of theactive compounds, without any need for the synergist added to be activeitself.

The active compound content of the use forms prepared from thecommercially available formulations may vary within wide limits. Theactive compound concentration of the application forms may be from0.00000001 to 95% by weight of active compound, preferably from 0.00001to 1% by weight.

The compounds are applied in a customary manner appropriate for the useforms.

The invention can be used to treat all plants and parts of plants.Plants in this context are understood to include all plants and plantpopulations, such as desired and unwanted wild plants or crop plants(including naturally occurring crop plants). Crop plants may be plantsobtainable by conventional breeding and optimization methods or bybiotechnological and gene-technological methods, or combinations ofthese methods, including the transgenic plants and including the plantcultivars protectable or not protectable by plant breeders' rights.Parts of plants shall be understood to mean all above-ground andbelow-ground parts and organs of plants, such as shoot, leaf, flower androot, examples including leaves, needles, stems, trunks, flowers, fruitbodies, fruits and seeds, and also roots, tubers and rhizomes. The plantparts also include harvested material and vegetative and generativepropagation material, for example cuttings, tubers, rhizomes, slips andseed.

The treatment according to the invention of the plants and plant partswith the active compounds is effected directly or by allowing them toact on the surroundings, habitat or storage space thereof by thecustomary treatment methods, for example by dipping, spraying,evaporating, fogging, scattering, painting on, injecting, and, in thecase of propagation material, especially in the case of seeds, also byapplying one or more coats.

As already mentioned above, it is possible to treat all plants and theirparts according to the invention. In a preferred embodiment, wild plantspecies and plant cultivars, or those obtained by conventionalbiological breeding, such as crossing or protoplast fusion, and partsthereof, are treated. In a further preferred embodiment, transgenicplants and plant cultivars obtained by genetic engineering methods, ifappropriate in combination with conventional methods (GeneticallyModified Organisms), and parts thereof are treated. The terms “parts” or“parts of plants” or “plant parts” have been explained above.

More preferably, plants of the plant cultivars which are eachcommercially available or in use are treated in accordance with theinvention. Plant cultivars are to be understood as meaning plants havingnew properties (“traits”) and which have been obtained by conventionalbreeding, by mutagenesis or by recombinant DNA techniques. They may becultivars, biotypes and genotypes.

In the animal health sector, i.e. in the field of veterinary medicine,the active compounds according to the present invention act againstanimal parasites, especially ectoparasites or endoparasites. The term“endoparasites” includes especially helminths such as cestodes,nematodes or trematodes, and protozoa such as coccidia. Ectoparasitesare typically and preferably arthropods, especially insects such asflies (biting and licking), parasitic fly larvae, lice, hair lice, birdlice, fleas and the like; or acaricides such as ticks, for example hardticks or soft ticks, or mites such as scab mites, harvest mites, birdmites and the like.

It has also been found that the compounds according to the inventionhave strong insecticidal action against insects which destroy industrialmaterials. Industrial materials in the present context are understood tomean inanimate materials, such as preferably plastics, adhesives, sizes,papers and cards, leather, wood, processed wood products and coatingcompositions.

In addition, the combinations according to the invention can be used asantifouling compositions, alone or in combinations with other activecompounds.

The active compounds are also suitable for controlling animal pests inthe domestic sector, in the hygiene sector and in the protection ofstored products, especially insects, arachnids and mites, which arefound in enclosed spaces, for example homes, factory halls, offices,vehicle cabins and the like. They can be used to control these pestsalone or in combination with other active compounds and auxiliaries indomestic insecticide products. They are effective against sensitive andresistant species, and against all developmental stages.

Plants are to be understood to mean all plant species, plant cultivarsand plant populations such as wanted and unwanted wild plants or cropplants. Crop plants to be treated according to the invention are plantswhich occur naturally or those which are obtained by conventionalbreeding and optimization methods or by biotechnological and recombinantmethods or by combining the methods mentioned above. The term crop plantdoes, of course, also include transgenic plants.

Plant cultivars are to be understood as meaning plants having newproperties (traits) and which have been obtained by conventionalbreeding, by mutagenesis or by recombinant DNA techniques or acombination thereof. They can be cultivars, varieties, bio- orgenotypes.

Plant parts are understood to mean all parts and organs of plants aboveand below the ground, such as shoot, leaf, flower and root, inparticular leaves, needles, stalks, stems, flowers, fruit bodies,fruits, seeds, roots, tubers and rhizomes. The term plant parts alsoincludes harvested material and vegetative and generative propagationmaterial, for example cuttings, tubers, rhizomes, slips and seeds orseed.

In a preferred embodiment, naturally occurring plant species and plantcultivars, or those obtained by conventional breeding and optimizationmethods (e.g. crossing or protoplast fusion), and also parts thereof,are treated.

In a further embodiment according to the invention, transgenic plantsobtained by genetic engineering methods, if appropriate in combinationwith conventional methods, and parts thereof are treated.

The treatment method according to the invention is preferably employedfor genetically modified organisms such as, for example, plants or plantparts.

Genetically modified plants, so-called transgenic plants, are plants inwhich a heterologous gene has been stably integrated into the genome.

The expression “heterologous gene” essentially means a gene which isprovided or assembled outside the plant and when introduced in thenuclear, chloroplastic or mitochondrial genome gives the transformedplant new or improved agronomic or other properties by expressing aprotein or polypeptide of interest or by downregulating or silencingother gene(s) which are present in the plant (using for example,antisense technology, cosuppression technology or RNAinterference—RNAi-technology). A heterologous gene that is located inthe genome is also called a transgene. A transgene that is defined byits particular location in the plant genome is called a transformationor transgenic event.

Depending on the plant species or plant cultivars, their location andgrowth conditions (soils, climate, vegetation period, diet), thetreatment according to the invention may also result in superadditive(“synergistic”) effects. Thus, for example, reduced application ratesand/or a widening of the activity spectrum and/or an increase in theactivity of the active compounds and compositions which can be usedaccording to the invention, better plant growth, increased tolerance tohigh or low temperatures, increased tolerance to drought or to water orsoil salt content, increased flowering performance, easier harvesting,accelerated maturation, higher harvest yields, bigger fruits, largerplant height, greener leaf colour, earlier flowering, higher qualityand/or a higher nutritional value of the harvested products, highersugar concentration within the fruits, better storage stability and/orprocessability of the harvested products are possible, which exceed theeffects which were actually to be expected.

At certain application rates, the active compound combinations accordingto the invention may also have a strengthening effect on plants.Accordingly, they are also suitable for mobilizing the defense system ofthe plant against attack by unwanted phytopathogenic fungi and/ormicroorganisms and or viruses. This may, if appropriate, be one of thereasons for the enhanced activity of the combinations according to theinvention, for example against fungi. Plant-strengthening(resistance-inducing) substances are to be understood as meaning, in thepresent context, those substances or combinations of substances whichare capable of stimulating the defense system of plants in such a waythat, when subsequently inoculated with unwanted phytopathogenic fungiand/or microorganisms and/or viruses, the treated plants display asubstantial degree of resistance to these unwanted phytopathogenic fungiand/or microorganisms and/or viruses. In the present case, unwantedphytopathogenic fungi and/or microorganisms and/or viruses areunderstood to mean phytopathogenic fungi, bacteria and viruses. Thus,the substances according to the invention can be employed for protectingplants against attack by the abovementioned pathogens within a certainperiod of time after the treatment. The period of time within whichprotection is effected generally extends from 1 to 10 days, preferably 1to 7 days, after the treatment of the plants with the active compounds.

Plants which are furthermore preferably treated according to theinvention are resistant against one or more biotic stress factors, i.e.said plants have a better defense against animal and microbial pests,such as against nematodes, insects, mites, phytopathogenic fungi,bacteria, viruses and/or viroids.

In addition to the plants and plant cultivars mentioned above, is alsopossible to treat those according to the invention which are resistantto one or more abiotic stress factors.

Abiotic stress conditions may include, for example, drought, coldtemperature exposure, heat exposure, osmotic stress, waterlogging,increased soil salinity, increased exposure to minerals, exposure toozone, exposure to strong light, limited availability of nitrogennutrients, limited availability of phosphorus nutrients or shadeavoidance.

Plants and plant varieties which may also be treated according to theinvention are those plants characterized by enhanced yieldcharacteristics. Enhanced yield in these plants may be the result of,for example, improved plant physiology, improved plant growth anddevelopment, such as water use efficiency, water retention efficiency,improved nitrogen use, enhanced carbon assimilation, improvedphotosynthesis, increased germination efficiency and acceleratedmaturation. Yield can also be affected by improved plant architecture(under stress and non-stress conditions), including early flowering,flowering control for hybrid seed production, seedling vigour, plantsize, internode number and distance, root growth, seed size, fruit size,pod size, pod or ear number, seed number per pod or ear, seed mass,enhanced seed filling, reduced seed dispersal, reduced pod dehiscenceand lodging resistance. Further yield traits include seed composition,such as carbohydrate content, protein content, oil content andcomposition, nutritional value, reduction in anti-nutritional compounds,improved processability and better storage stability.

Plants that may be treated according to the invention are hybrid plantsthat already express the characteristic of heterosis or hybrid vigorwhich results in generally higher yield, vigor, health and resistancetowards biotic and abiotic stresses. Such plants are typically made bycrossing an inbred male-sterile parent line (the female parent) withanother inbred male-fertile parent line (the male parent). Hybrid seedis typically harvested from the male sterile plants and sold to growers.Male sterile plants can sometimes (e.g. in maize) be produced bydetasseling, (i.e. the mechanical removal of the male reproductiveorgans or male flowers) but, more typically, male sterility is theresult of genetic determinants in the plant genome. In that case, andespecially when seed is the desired product to be harvested from thehybrid plants it is typically useful to ensure that male fertility inthe hybrid plants which contain the genetic determinants responsible formale sterility is fully restored. This can be accomplished by ensuringthat the male parents have appropriate fertility restorer genes whichare capable of restoring the male fertility in hybrid plants thatcontain the genetic determinants responsible for male sterility. Geneticdeterminants for male sterility may be located in the cytoplasm.Examples of cytoplasmic male sterility (CMS) were for instance describedfor Brassica species. However, genetic determinants for male sterilitycan also be located in the nuclear genome. Male-sterile plants can alsobe obtained by plant biotechnology methods such as genetic engineering.A particularly useful means of obtaining male-sterile plants isdescribed in WO 89/10396, in which, for example, a ribonuclease such asa barnase is selectively expressed in the tapetum cells in the stamens.Fertility can then be restored by expression in the tapetum cells of aribonuclease inhibitor such as barstar.

Plants or plant cultivars (obtained by plant biotechnology methods suchas genetic engineering) which may be treated according to the inventionare herbicide-tolerant plants, i.e. plants made tolerant to one or moregiven herbicides. Such plants can be obtained either by genetictransformation, or by selection of plants containing a mutationimparting such herbicide tolerance.

Herbicide-tolerant plants are for example glyphosate-tolerant plants,i.e. plants made tolerant to the herbicide glyphosate or salts thereof.For example, glyphosate-tolerant plants can be obtained by transformingthe plant with a gene encoding the enzyme5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Examples of suchEPSPS genes are the AroA gene (mutant CT7) of the bacterium Salmonellatyphimurium, the CP4 gene of the bacterium Agrobacterium sp., the genesencoding a petunia EPSPS, a tomato EPSPS, or an Eleusine EPSPS. It canalso be a mutated EPSPS. Glyphosate-tolerant plants can also be obtainedby expressing a gene that encodes a glyphosate oxido-reductase enzyme.Glyphosate-tolerant plants can also be obtained by expressing a genethat encodes a glyphosate acetyl transferase enzyme. Glyphosate-tolerantplants can also be obtained by selecting plants containingnaturally-occurring mutations of the above-mentioned genes.

Other herbicide resistant plants are for example plants that are madetolerant to herbicides inhibiting the enzyme glutamine synthase, such asbialaphos, phosphinothricin or glufosinate. Such plants can be obtainedby expressing an enzyme detoxifying the herbicide or a mutant glutaminesynthase enzyme that is resistant to inhibition. One such efficientdetoxifying enzyme is an enzyme encoding a phosphinothricinacetyltransferase (such as the bar or pat protein from Streptomycesspecies). Plants expressing an exogenous phosphinothricinacetyltransferase have been described.

Further herbicide-tolerant plants are also plants that have been madetolerant to the herbicides inhibiting the enzyme hydroxyphenylpyruvatedioxygenase (HPPD). Hydroxyphenylpyruvate dioxygenases are enzymes thatcatalyze the reaction in which para-hydroxyphenylpyruvate (HPP) isconverted to homogentisate. Plants tolerant to HPPD inhibitors can betransformed with a gene encoding a naturally-occurring resistant HPPDenzyme, or a gene encoding a mutated HPPD enzyme. Tolerance to HPPDinhibitors can also be obtained by transforming plants with genesencoding certain enzymes enabling the formation of homogentisate despitethe inhibition of the native HPPD enzyme by the HPPD inhibitor.Tolerance of plants to HPPD inhibitors can also be improved bytransforming plants with a gene encoding an enzyme prephenatedeshydrogenase in addition to a gene encoding an HPPD-tolerant enzyme.

Still further herbicide resistant plants are plants that are madetolerant to acetolactate synthase (ALS) inhibitors. Known ALS inhibitorsinclude, for example, sulphonylurea, imidazolinone, triazolopyrimidines,pyrimidinyoxy(thio)benzoates, and/or sulphonylaminocarbonyltriazolinoneherbicides. Different mutations in the ALS enzyme (also known asacetohydroxyacid synthase, AHAS) are known to confer tolerance todifferent herbicides and groups of herbicides. The production ofsulphonylurea-tolerant plants and imidazolinone-tolerant plants has beendescribed in the international publication WO 1996/033270. Furthersulphonylurea- and imidazolinone-tolerant plants have also beendescribed, for example in WO 2007/024782.

Other plants tolerant to imidazolinone and/or sulphonylurea can beobtained by induced mutagenesis, selection in cell cultures in thepresence of the herbicide or mutation breeding.

Plants or plant cultivars (obtained by plant biotechnology methods suchas genetic engineering) which may also be treated according to theinvention are insect-resistant transgenic plants, i.e. plants maderesistant to attack by certain target insects. Such plants can beobtained by genetic transformation, or by selection of plants containinga mutation imparting such insect resistance.

An “insect-resistant transgenic plant”, as used herein, includes anyplant containing at least one transgene comprising a coding sequenceencoding:

-   1) an insecticidal crystal protein from Bacillus thuringiensis or an    insecticidal portion thereof, such as the insecticidal crystal    proteins described online at:    http://www.lifesci.sussex.ac.uk/Home/Neil_Crickmore/Bt/, or    insecticidal portions thereof, e.g., proteins of the Cry protein    classes Cry1Ab, Cry1Ac, Cry1F, Cry2Ab, Cry3Ae, or Cry3Bb or    insecticidal portions thereof; or-   2) a crystal protein from Bacillus thuringiensis or a portion    thereof which is insecticidal in the presence of a second other    crystal protein from Bacillus thuringiensis or a portion thereof,    such as the binary toxin made up of the Cry34 and Cry35 crystal    proteins; or-   3) a hybrid insecticidal protein comprising parts of two different    insecticidal crystal proteins from Bacillus thuringiensis, such as a    hybrid of the proteins of 1) above or a hybrid of the proteins of 2)    above, e.g., the Cry1A.105 protein produced by maize event MON89034    (WO 2007/027777); or-   4) a protein of any one of 1) to 3) above wherein some, particularly    1 to 10, amino acids have been replaced by another amino acid to    obtain a higher insecticidal activity to a target insect species,    and/or to expand the range of target insect species affected, and/or    because of changes induced into the encoding DNA during cloning or    transformation, such as the Cry3Bb1 protein in maize events MON863    or MON88017, or the Cry3A protein in maize event MIR604; or-   5) an insecticidal secreted protein from Bacillus thuringiensis or    Bacillus cereus, or an insecticidal portion thereof, such as the    vegetative insecticidal proteins (VIP) listed at:    http://www.lifesci.sussex.ac.uk/Home/Neil_Crickmore/Bt/vip.html, for    example proteins from the VIP3Aa protein class; or-   6) a secreted protein from Bacillus thuringiensis or Bacillus cereus    which is insecticidal in the presence of a second secreted protein    from Bacillus thuringiensis or B. cereus, such as the binary toxin    made up of the VIP1A and VIP2A proteins;-   7) a hybrid insecticidal protein comprising parts from different    secreted proteins from Bacillus thuringiensis oder Bacillus cereus,    such as a hybrid of the proteins in 1) above or a hybrid of the    proteins in 2) above; or-   8) a protein of any one of 1) to 3) above wherein some, particularly    1 to 10, amino acids have been replaced by another amino acid to    obtain a higher insecticidal activity to a target insect species,    and/or to expand the range of target insect species affected, and/or    because of changes induced into the encoding DNA during cloning or    transformation (while still encoding an insecticidal protein), such    as the VIP3Aa protein in cotton event COT102.

Of course, an insect-resistant transgenic plant, as used herein, alsoincludes any plant comprising a combination of genes encoding theproteins of any one of the above classes 1 to 8. In one embodiment, aninsect-resistant plant contains more than one transgene encoding aprotein of any one of the above classes 1 to 8, to expand the range oftarget insect species affected, or to delay insect resistancedevelopment to the plants by using different proteins insecticidal tothe same target insect species but having a different mode of action,such as binding to different receptor binding sites in the insect.

Plants or plant cultivars (obtained by plant biotechnology methods suchas genetic engineering) which may also be treated according to theinvention are tolerant to abiotic stresses. Such plants can be obtainedby genetic transformation, or by selection of plants containing amutation imparting such stress resistance. Particularly useful stresstolerance plants include:

-   a. plants which contain a transgene capable of reducing the    expression and/or the activity of the poly(ADP-ribose) polymerase    (PARP) gene in the plant cells or plants;-   b. plants which contain a stress tolerance enhancing transgene    capable of reducing the expression and/or the activity of the PARG    encoding genes of the plants or plants cells;-   c. plants which contain a stress tolerance-enhancing transgene    coding for a plant-functional enzyme of the nicotinamide adenine    dinucleotide salvage biosynthesis pathway, including nicotinamidase,    nicotinate phosphoribosyltransferase, nicotinic acid mononucleotide    adenyltransferase, nicotinamide adenine dinucleotide synthetase or    nicotinamide phosphoribosyltransferase.

Plants or plant varieties (obtained by plant biotechnology methods suchas genetic engineering) which may also be treated according to theinvention show altered quantity, quality and/or storage stability of theharvested product and/or altered properties of specific ingredients ofthe harvested product such as, for example:

-   1) transgenic plants which synthesize a modified starch, which in    its physical-chemical characteristics, in particular the amylose    content or the amylose/amylopectin ratio, the degree of branching,    the average chain length, the side chain distribution, the viscosity    behaviour, the gelling strength, the starch grain size and/or the    starch grain morphology, is changed in comparison with the    synthesised starch in wild type plant cells or plants, so that this    is better suited for special applications.-   2) transgenic plants which synthesize non starch carbohydrate    polymers or which synthesize non starch carbohydrate polymers with    altered properties in comparison to wild type plants without genetic    modification. Examples are plants which produce polyfructose,    especially of the inulin and levan type, plants which produce    alpha-1,4-glucans, plants which produce alpha-1,6-branched    alpha-1,4-glucans, and plants producing alternan.-   3) Transgenic plants which produce hyaluronan.

Plants or plant cultivars (obtained by plant biotechnology methods suchas genetic engineering) which may also be treated according to theinvention are plants, such as cotton plants, with altered fibrecharacteristics. Such plants can be obtained by genetic transformation,or by selection of plants containing a mutation imparting such alteredfibre characteristics and include:

-   a) plants, such as cotton plants, containing an altered form of    cellulose synthase genes;-   b) plants, such as cotton plants, containing an altered form of rsw2    or rsw3 homologous nucleic acids;-   c) plants, such as cotton plants, with increased expression of    sucrose phosphate synthase;-   d) plants, such as cotton plants, with increased expression of    sucrose synthase;-   e) plants, such as cotton plants, wherein the timing of the    plasmodesmatal gating at the basis of the fibre cell is altered, for    example through downregulation of fibre-selective β-1,3-glucanase;-   f) plants, such as cotton plants, having fibres with altered    reactivity, e.g. through the expression of    N-acetylglucosaminetransferase gene including nodC and chitin    synthase genes.

Plants or plant cultivars (that can be obtained by plant biotechnologymethods such as genetic engineering) which may also be treated accordingto the invention are plants, such as oilseed rape or related Brassicaplants, with altered oil profile characteristics. Such plants can beobtained by genetic transformation, or by selection of plants containinga mutation imparting such altered oil profile characteristics andinclude:

-   a) plants, such as oilseed rape plants, which produce oil having a    high oleic acid content;-   b) plants, such as oilseed rape plants, which produce oil having a    low linolenic acid content;-   c) plants, such as oilseed rape plants, producing oil having a low    level of saturated fatty acids.

Particularly useful transgenic plants which may be treated according tothe invention are plants which comprise one or more genes which encodeone or more toxins, and are the transgenic plants which are sold underthe following trade names: YIELD GARD® (for example maize, cotton, soyabeans), KnockOut® (for example maize), BiteGard® (for example maize),BT-Xtra® (for example maize), StarLink® (for example maize), Bollgard®(cotton), Nucotn® (cotton), Nucotn 33B® (cotton), NatureGard® (forexample maize), Protecta® and NewLeaf® (potato). Examples ofherbicide-tolerant plants which should be mentioned are maize varieties,cotton varieties and soya bean varieties which are available under thefollowing trade names: Roundup Ready® (tolerance to glyphosate, forexample maize, cotton, soya beans), Liberty Link® (tolerance tophosphinothricin, for example oilseed rape), IMI® (tolerance toimidazolinone) and SCS® (tolerance to sulphonylurea, for example maize).Herbicide-resistant plants (plants bred in a conventional manner forherbicide tolerance) which may be mentioned include the varieties soldunder the name Clearfield® (for example maize).

Particularly useful transgenic plants which may be treated according tothe invention are plants containing transformation events, or acombination of transformation events, and that are listed for example inthe databases for various national or regional regulatory agencies (seefor example http://gmoinfo.jrc.it/gmp_browse.aspx andhttp://www.agbios.com/dbase.php).

Treatment according to the invention of the plants and plant parts withthe active compound combinations is carried out directly or by allowingthe compounds to act on their surroundings, environment or storage spaceby the customary treatment methods, for example by immersion, spraying,evaporation, fogging, scattering, painting on and, in the case ofpropagation material, in particular in the case of seeds, also byapplying one or more coats.

The mixtures according to the invention are particularly suitable forthe treatment of seed. Here, particular mention may be made of thecombinations according to the invention mentioned above as preferred orparticularly preferred. Thus, most of the damage to crop plants which iscaused by pests occurs as early as when the seed is infested duringstorage and after the seed is introduced into the soil, and during andimmediately after germination of the plants. This phase is particularlycritical since the roots and shoots of the growing plant areparticularly sensitive and even minor damage can lead to the death ofthe whole plant. Protecting the seed and the germinating plant by theuse of suitable compositions is therefore of particularly greatinterest.

The control of pests by treating the seed of plants has been known for along time and is the subject of continuous improvements. However, thetreatment of seed entails a series of problems which cannot always besolved in a satisfactory manner. Thus, it is desirable to developmethods for protecting the seed and the germinating plant which dispensewith the additional application of crop protection compositions aftersowing or after emergence of the plants. It is furthermore desirable tooptimize the amount of active compound employed in such a way as toprovide optimum protection for the seed and the germinating plant fromattack by pests, but without damaging the plant itself by the activecompound employed. In particular, methods for the treatment of seedshould also take into consideration the intrinsic insecticidalproperties of transgenic plants in order to achieve optimum protectionof the seed and the germinating plant with a minimum of crop protectioncompositions being employed.

The present invention therefore in particular also relates to a methodfor the protection of seed and germinating plants, from attack by pests,by treating the seed with a composition according to the invention. Theinvention likewise relates to the use of the compositions according tothe invention for the treatment of seed for protecting the seed and theresulting plant from pests. The invention further relates to seed whichhas been treated with a composition according to the invention forprotection from pests.

One of the advantages of the present invention is that the particularsystemic properties of the compositions according to the invention meanthat treatment of the seed with these compositions not only protects theseed itself, but also the resulting plants after emergence, from pests.In this way, the immediate treatment of the crop at the time of sowingor shortly thereafter can be dispensed with.

A further advantage is the synergistically increased insecticidalactivity of the compositions according to the invention in comparisonwith the individual insecticidally active compound, which exceeds theexpected activity of the two active compounds when applied individually.Also advantageous is the synergictic enhancement of the fungicidalactivity of the compositions according to the invention compared withthe individual fungicidally active compound, which exceeds the expectedactivity of the active compound applied individually. This makespossible an optimization of the amount of active compounds employed.

Furthermore, it must be considered as advantageous that the mixturesaccording to the invention can also be employed in particular intransgenic seed, the plants arising from this seed being capable ofexpressing a protein directed against pests. By treating such seed withthe compositions according to the invention, certain pests can becontrolled merely by the expression of the, for example, insecticidalprotein, and additionally damage to the seed may be averted by thecompositions according to the invention.

The compositions according to the invention are suitable for protectingseed of any plant variety as already mentioned above which is employedin agriculture, in the greenhouse, in forests or in horticulture. Inparticular, this takes the form of seed of maize, peanut, canola,oilseed rape, poppy, soya beans, cotton, beet (for example sugar beetand fodder beet), rice, millet, wheat, barley, oats, rye, sunflower,tobacco, potatoes or vegetables (for example tomatoes, cabbage species).The compositions according to the invention are likewise suitable fortreating the seed of fruit plants and vegetables as already mentionedabove. The treatment of the seed of maize, soya beans, cotton, wheat andcanola or oilseed rape is of particular importance.

As already mentioned above, the treatment of transgenic seed with acomposition according to the invention is also of particularsignificance. This takes the form of seed of plants which, as a rule,comprise at least one heterologous gene which governs the expression ofa polypeptide with in particular insecticidal properties. In thiscontext, the heterologous genes in transgenic seed may be derived frommicroorganisms such as Bacillus, Rhizobium, Pseudomonas, Serratia,Trichoderma, Clavibacter, Glomus or Gliocladium. The present inventionis particularly suitable for the treatment of transgenic seed whichcomprises at least one heterologous gene originating from Bacillus sp.and whose gene product shows activity against the European corn borerand/or the corn root worm. The gene involved is more preferably aheterologous gene which originates from Bacillus thuringiensis.

Within the context of the present invention, the composition accordingto the invention is applied to the seed either alone or in a suitableformulation. Preferably, the seed is treated in a state in which it isstable enough to avoid damage during treatment. In general, the seed maybe treated at any point in time between harvest and sowing. The seedusually used has been separated from the plant and freed from cobs,shells, stalks, coats, hairs or the flesh of the fruits.

When treating the seed, it generally has to be ensured that the amountof the composition according to the invention applied to the seed and/orthe amount of further additives is selected such that the germination ofthe seed is not impaired, or that the resulting plant is not damaged.This must be ensured particularly in the case of active compounds whichcan exhibit phytotoxic effects at certain application rates.

In addition, the compounds according to the invention can be used tocontrol a multitude of different pests, including, for example, harmfulsucking insects, biting insects and other pests which are plantparasites, stored material pests, pests which destroy industrialmaterial, and hygiene pests including parasites in the animal healthsector, and for the control thereof, for example the elimination anderadication thereof. The present invention thus also includes a methodfor controlling pests.

In the animal health sector, i.e. in the field of veterinary medicine,the active compounds according to the present invention act againstanimal parasites, especially ectoparasites or endoparasites. The term“endoparasites” includes especially helminths such as cestodes,nematodes or trematodes, and protozoa such as coccidia. Ectoparasitesare typically and preferably arthropods, especially insects such asflies (biting and licking), parasitic fly larvae, lice, hair lice, birdlice, fleas and the like; or acaricides such as ticks, for example hardticks or soft ticks, or mites such as scab mites, harvest mites, birdmites and the like.

These parasites include:

From the order of the Anoplurida, for example, Haematopinus spp.,Linognathus spp., Pediculus spp., Phthirus spp. and Solenopotes spp.;specific examples are: Linognathus setosus, Linognathus vituli,Linognathus ovillus, Linognathus oviformis, Linognathus pedalis,Linognathus stenopsis, Haematopinus asini macrocephalus, Haematopinuseurysternus, Haematopinus suis, Pediculus humanus capitis, Pediculushumanus corporis, Phylloera vastatrix, Phthirus pubis, Solenopotescapillatus;

From the order of the Mallophagida and the suborders Amblycerina andIschnocerina, for example, Trimenopon spp., Menopon spp., Trinoton spp.,Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp.,Trichodectes spp. and Felicola spp.; specific examples are: Bovicolabovis, Bovicola ovis, Bovicola limbata, Damalina bovis, Trichodectescanis, Felicola subrostratus, Bovicola caprae, Lepikentron ovis,Werneckiella equi;

From the order of the Diptera and the suborders Nematocerina andBrachycerina, for example, Aedes spp., Anopheles spp., Culex spp.,Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp.,Culicoides spp., Chrysops spp., Odagmia spp., Wilhelmia spp., Hybomitraspp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp.,Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp.,Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Luciliaspp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp.,Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp.,Melophagus spp., Rhinoestrus spp., Tipula spp.; specific examples are:Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anophelesgambiae, Anopheles maculipennis, Calliphora erythrocephala, Chrysozonapluvialis, Culex quinquefasciatus, Culex pipiens, Culex tarsalis, Fanniacanicularis, Sarcophaga carnaria, Stomoxys calcitrans, Tipula paludosa,Lucilia cuprina, Lucilia sericata, Simulium reptans, Phlebotomuspapatasi, Phlebotomus longipalpis, Odagmia ornata, Wilhelmia equina,Boophthora erythrocephala, Tabanus bromius, Tabanus spodopterus, Tabanusatratus, Tabanus sudeticus, Hybomitra ciurea, Chrysops caecutiens,Chrysops relictus, Haematopota pluvialis, Haematopota italica, Muscaautumnalis, Musca domestica, Haematobia irritans irritans, Haematobiairritans exigua, Haematobia stimulans, Hydrotaea irritans, Hydrotaeaalbipuncta, Chrysomya chloropyga, Chrysomya bezziana, Oestrus ovis,Hypoderma bovis, Hypoderma lineatum, Przhevalskiana silenus, Dermatobiahominis, Melophagus ovinus, Lipoptena capreoli, Lipoptena cervi,Hippobosca variegata, Hippobosca equina, Gasterophilus intestinalis,Gasterophilus haemorroidalis, Gasterophilus inermis, Gasterophilusnasalis, Gasterophilus nigricornis, Gasterophilus pecorum, Braula coeca;

From the order of the Siphonapterida, for example Pulex spp.,Ctenocephalides spp., Tunga spp., Xenopsylla spp., Ceratophyllus spp.;specific examples are: Ctenocephalides canis, Ctenocephalides felis,Pulex irritans, Tunga penetrans, Xenopsylla cheopis;

From the order of the Heteropterida, for example, Cimex spp., Triatomaspp., Rhodnius spp. and Panstrongylus spp.

From the order of the Blattarida, for example Blatta orientalis,Periplaneta americana, Blattela germanica and Supella spp. (e.g.Suppella longipalpa);

From the subclass of the Acari (Acarina) and the orders of the Meta- andMesostigmata, for example, Argas spp., Ornithodorus spp., Otobius spp.,Ixodes spp., Amblyomma spp., Rhipicephalus (Boophilus) spp., Dermacentorspp., Haemophysalis spp., Hyalomma spp., Dermanyssus spp., Rhipicephalusspp. (the original genus of multihost ticks), Ornithonyssus spp.,Pneumonyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp.,Varroa spp., Acarapis spp.; specific examples are: Argas persicus, Argasreflexus, Ornithodorus moubata, Otobius megnini, Rhipicephalus(Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus,Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus)calceratus, Hyalomma anatolicum, Hyalomma aegypticum, Hyalommamarginatum, Hyalomma transiens, Rhipicephalus evertsi, Ixodes ricinus,Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, Ixodes rubicundus,Ixodes scapularis, Ixodes holocyclus, Haemaphysalis concinna,Haemaphysalis punctata, Haemaphysalis cinnabarina, Haemaphysalisotophila, Haemaphysalis leachi, Haemaphysalis longicorni, Dermacentormarginatus, Dermacentor reticulatus, Dermacentor pictus, Dermacentoralbipictus, Dermacentor andersoni, Dermacentor variabilis, Hyalommamauritanicum, Rhipicephalus sanguineus, Rhipicephalus bursa,Rhipicephalus appendiculatus, Rhipicephalus capensis, Rhipicephalusturanicus, Rhipicephalus zambeziensis, Amblyomma americanum, Amblyommavariegatum, Amblyomma maculatum, Amblyomma hebraeum, Amblyommacajennense, Dermanyssus gallinae, Ornithonyssus bursa, Ornithonyssussylviarum, Varroa jacobsoni;

From the order of the Actinedida (Prostigmata) and Acaridida(Astigmata), for example, Acarapis spp., Cheyletiella spp.,Ornithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp.,Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp.,Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp.,Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp.,Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.; specificexamples are: Cheyletiella yasguri, Cheyletiella blakei, Demodex canis,Demodex bovis, Demodex ovis, Demodex caprae, Demodex equi, Demodexcaballi, Demodex suis, Neotrombicula autumnalis, Neotrombicula desaleri,Neoschongastia xerothermobia, Trombicula akamushi, Otodectes cynotis,Notoedres cati, Sarcoptis canis, Sarcoptes bovis, Sarcoptes ovis,Sarcoptes rupicaprae (=S. caprae), Sarcoptes equi, Sarcoptes suis,Psoroptes ovis, Psoroptes cuniculi, Psoroptes equi, Chorioptes bovis,Psoergates ovis, Pneumonyssoidic mange, Pneumonyssoides caninum,Acarapis woodi.

The active compounds according to the invention are also suitable forcontrolling arthropods, helminths and protozoa which attack animals. Theanimals include agricultural livestock, for example cattle, sheep,goats, horses, pigs, donkeys, camels, buffalo, rabbits, chickens,turkeys, ducks, geese, cultured fish, honey bees. The animals alsoinclude domestic animals—also referred to as companion animals—forexample dogs, cats, caged birds, aquarium fish, and what are known astest animals, for example hamsters, guinea pigs, rats and mice.

The control of these arthropods, helminths and/or protozoa should reducecases of death and improve the performance (for meat, milk, wool, hides,eggs, honey etc.) and the health of the host animal, and so the use ofthe active compounds according to the invention enables moreeconomically viable and easier animal husbandry.

For example, it is desirable to prevent or to interrupt the uptake ofblood from the host by the parasites (if relevant). Control of theparasites can also contribute to preventing the transmission ofinfectious substances.

The term “control” as used herein with regard to the field of animalhealth means that the active compounds act by reducing the occurrence ofthe parasite in question in an animal infested with such parasites to aharmless level. More specifically, “control” as used herein means thatthe active compound kills the parasite in question, retards its growthor inhibits its proliferation.

In general, the active compounds according to the invention can beemployed directly when they are used for the treatment of animals. Theyare preferably employed in the form of pharmaceutical compositions whichmay comprise the pharmaceutically acceptable excipients and/orauxiliaries known in the prior art.

In the sector of animal health and in animal husbandry, the activecompounds are employed (administered) in a known manner, by enteraladministration in the form of, for example, tablets, capsules, potions,drenches, granules, pastes, boluses, the feed-through process andsuppositories, by parenteral administration, for example by injection(intramuscular, subcutaneous, intravenous, intraperitoneal inter alia),implants, by nasal administration, by dermal administration in the form,for example, of dipping or bathing, spraying, pouring on and spottingon, washing and powdering, and also with the aid of moulded articlescontaining the active compound, such as collars, earmarks, tailmarks,limb bands, halters, marking devices, etc. The active compounds can beformulated as a shampoo or as suitable formulations applicable inaerosols or unpressurized sprays, for example pump sprays and atomizersprays,

In the case of employment for livestock, poultry, domestic pets, etc.,the active compounds according to the invention can be employed asformulations (for example powders, wettable powders [“WP”], emulsions,emulsifiable concentrates [“EC”], free-flowing compositions, homogeneoussolutions and suspension concentrates [“SC”]), which contain the activecompounds in an amount of 1 to 80% by weight, directly or after dilution(e.g. 100- to 10 000-fold dilution), or they can be used as a chemicalbath.

In the case of use in the animal health sector, the active compoundsaccording to the invention can be used in combination with suitablesynergists or other active compounds, for example acaricides,insecticides, anthelmintics, anti-protozoal agents.

The compounds according to the invention can be prepared by customarymethods known to those skilled in the art.

Reaction Scheme 1 shows the general Preparation Process A for thecompounds (I) according to the invention.

The radicals A₁-A₄, Q, W, R¹ and R⁶ have the meanings described above. Trepresents the grouping

where the radicals Z¹, Z² and Z³ have the meaning given above and theasterisk represents the point of attachment to the grouping C═W. X isany leaving group.

Compounds according to the invention of type (I) can be prepared byreacting amines of the general structure (IV) with activated carboxylicacid derivatives of the general structure (V). The reaction can becarried out in the presence or absence of a solvent. In this step, it isalso possible to employ a suitable base.

In general, it is advantageous to carry out the first reaction step ofPreparation Process A according to the invention, if appropriate, in thepresence of a suitable diluent and, if appropriate, in the presence of asuitable basic reaction auxiliary.

Diluents are advantageously employed in such an amount that the reactionmixture remains readily stirrable during the entire process.

Suitable for use as solvent are any solvents which do not interfere withthe reaction such as, for example, water. Suitable are aromatichydrocarbons such as benzene or toluene; halogenated hydrocarbons suchas dichloromethane, chloroform or carbon tetrachloride, open-chain orcyclic ethers such as diethyl ether, dioxane, tetrahydrofuran or1,2-dimethoxyethane; esters such as ethyl acetate and butyl acetate;ketones such as, for example, acetone, methyl isobutyl ketone andcyclohexanone; amides such as dimethylformamide and dimethylacetamide;nitriles such as acetonitrile; and other inert solvents such as1,3-dimethyl-2-imidazolidinone; the solvents can be employed on theirown or in a combination of two or more solvents.

The base used can be an organic base such as triethylamine,ethyldiisopropylamine, tri-n-butylamine, pyridine and4-dimethylaminopyridine; furthermore, it is possible to use, forexample, the following bases: alkali metal hydroxides such as, forexample, sodium hydroxide and potassium hydroxide; carbonates such assodium bicarbonate and potassium carbonate; phosphates such asdipotassium hydrogenphosphate and trisodium phosphate; alkali metalhydrides such as sodium hydride; alkali metal alkoxides such as sodiummethoxide and sodium ethoxide. These bases can be employed in ratios offrom 0.01 to 5.0 molar equivalents based on (IV) and (V). Furthermore,it is also possible to use silver(I) cyanide as base and activator[Journal of Organic Chemistry. 1992, 57, 4394-4400; Journal of MedicinalChemistry 1992, 35, 3905-3918; Journal of Organic Chemistry 2003, 68,1843-1851]

The suitable reaction temperature is in the range from −20° C. to theboiling point of the solvent in question and the reaction time is from afew minutes to 96 hours, depending on the chosen reactants, solvents andreaction temperature.

Cyclic carbonyl halides as represented by the general structure (V) canbe prepared in a simple manner by reacting a heterocyclic carboxylicacid with halogenating agents such as thionyl chloride, thionyl bromide,phosphoryl chloride, oxalyl chloride, phosphorus trichloride, etc.[Houben-Weyl, 1952, Vol. VIII, p. 463 ff.].

However, the preparation of carboxamides represented by formula (I) canalso be carried out using coupling reagents such asdicyclohexylcarbodiimide and additives such as 1-hydroxybenzotriazole[Chem. Ber. 1970, 788]. It is also possible to use coupling reagentssuch as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide,1,1′-carbonyl-1H-imidazole and similar compounds.

The coupling reagents used to perform the preparation process are allwhich are suitable for forming an ester or amide bond (cf. for example,Bodansky et al., Peptide Synthesis, 2nd ed., Wiley & Sons, New York,1976; Gross, Meienhofer, The Peptide: Analysis, Synthesis, Biology,Academic Press, New York, 1979).

Furthermore, it is also possible to use mixed anhydrides for preparing(I) [J. Am. Chem. Soc 1967, 5012]. In this process, it is possible touse various chloroformic esters, for example isobutyl chloroformate,isopropyl chloroformate. It is likewise possible for this purpose to usediethylacetyl chloride, trimethylacetyl chloride and the like.

Compounds of the general structure (IV) can be prepared by reacting anamine of the general structure (III) with activated carboxylic acidderivatives of the general structure (II). Here, the same conditions asin the preparation of (I) described above apply with respect to thechoice of solvent, reaction conditions, reaction time and reagents.

Reaction Scheme 2 shows the general Preparation Process B for thesynthesis of the compounds (I) according to the invention.

The radicals A₁-A₄, Q, R¹, R⁶ and W have the meanings described above. Xrepresents any leaving group and Alk represents an alkyl radical suchas, for example, methyl or ethyl. T represents the grouping

where the radicals Z¹, Z² and Z³ have the meaning given above and theasterisk represents the point of attachment to the grouping C═W.

Compounds according to the invention of type (I) can be prepared byreacting an amine of the general structure (III) with activatedcarboxylic acid derivatives of the general structure (VIII). Here, thesame conditions as in the conversion of (IV) and (V) into (I) describedin Preparation Process A apply with respect to the choice of solvent,reaction conditions, reaction time and reagents.

Activated carboxylic acid derivatives of the general structure (VIII)can be prepared by a two-step synthesis from the correspondingcarboxylic esters of the general structure (VII). In the first step, thecarboxylic acid function, protected in the form of an ester (O-Alk), ofthe compound (VII) is, depending on the alkyl ester used, deprotectedwith a suitable reagent [Greene's protective groups in organicsynthesis, 4. Edition, P. G. M. Wuts, T. W. Greene, John Wiley & Sons,Inc., Hoboken, N.J.], and the resulting free hydroxyl group of the acidfunction of (VIII-1) is converted into a leaving group X. Here, the sameprocesses as already described for the preparation of (V) may beemployed. Compounds of the general structure (VII) can be prepared byreacting amines of the general structure (VI) with activated carboxylicacid derivatives of the general structure (V). Here, the same conditionsas in the synthesis of (I) described in Preparation Process A apply withrespect to the choice of solvent, reaction conditions, reaction time andreagents.

Reaction Scheme 3 shows the general Preparation Process C for thesynthesis of the compounds (I) according to the invention.

The radicals A₁-A₄, Q, R⁶ and W have the meanings described above. Xrepresents any leaving group such as, for example, chlorine, bromine oriodine. T represents the grouping

where the radicals Z¹, Z² and Z³ have the meaning given above and theasterisk represents the point of attachment to the grouping C═W. R¹represents the radicals described above except for hydrogen. Thecompounds of the general structure (I) where R1≠H can be prepared fromcompounds of the general structure (I-1). Here, use may be made ofprocesses known from the literature [R1=optionally subst. alkyl &(het)arylalkyl: WO2008/061688; Journal of Heterocyclic Chemistry 1995,32(3), 835-839; WO2011/029808; WO2010/020432; US2010/0152192;WO2010/101949; WO2010/043377, Medicinal Chemistry Letters 2011, 2(8),632-637; Journal of Heterocyclic Chemistry 1977, 14(7), 1263-1265;WO2011/020193; WO2008/121602; WO2006/074924; WO2006/065794|R¹=optionallysubst. alkylcarbony & (het)aryl(alkyl)carbonyl: WO2010/015545; Journalof the Chemical Society, Perkin Transactions 1 2002, (2), 257-274; U.S.Pat. No. 7,951,828|R1=optionally subst. alkoxycarbonyl &(het)aryl(alkyl)oxycarbonyl: WO2011/112731; WO2009/027393; Journal ofOrganic Chemistry 2011, 76(8), 2502-2520|R1=optionally subst. alkynyl:Synthesis 2007, (18), 2920-2923; Tetrahedron 2006, 62(16), 3856-3871;Journal of the American Chemical Society 2006, 128(14), 4586-4587;Chemical Communications (Cambridge, United Kingdom) 2010, 46(8),1269-1271; WO2009/027393|R1=optionally subst. alkenyl: OrganicChemistry: An Indian Journal 2010, 6(1), 52-55; European Journal ofOrganic Chemistry 2009, (1), 72-84; WO2006/067444; WO2005/049585].

Reaction Scheme 4 shows the general Preparation Process D for thesynthesis of the compounds (I) according to the invention.

The radicals A₁-A₄, Q, R¹ and W have the meanings described above. Xrepresents any leaving group such as, for example, chlorine, bromine oriodine. T represents the grouping

where the radicals Z¹, Z² and Z³ have the meaning given above and theasterisk represents the point of attachment to the grouping C═W. R⁶represents the radicals described above.

The compounds of the general structure (I) can be prepared fromcompounds of the general structure (1-1). Here, use may be made of theprocesses mentioned for Preparation Process C.

Compounds of the general formulae (II-1), (II-1-1) and (II-2) can beused as precursors for the substances of the general formula (II).Substances of the general formula (II-1-1) are generally known compoundsof organic chemistry which can be obtained by established synthesisprocesses. Possible synthesis routes for the cyclic aminocarboxylicacids of the general formula (II-1-1) are shown in Reaction Scheme 5.

Halogenated (hetero)aromatic nitro- or amino compounds, for example, asrepresented by the formulae (IX) and (XIV) may serve as startingmaterials for preparing aminocarboxylic acids of the general structure(II-1-1). Here, the leaving group X is replaced by a cyano group, andthe latter is then subjected to acidic or basic hydrolysis. Thehalogen/cyano exchange can be effected, for example, by nucleophilicsubstitution at the aromatic ring using a cyanide species such as, forexample, sodium cyanide [U.S. Pat. No. 4,766,219], or else by acopper-mediated reaction [Journal of Antibiotics 1994, 47(12), 1456-65].

In the case of the nitro compounds (IX, X, and XIII), the nitro functionmay subsequently be reduced to an amino function. Suitable processes forsuch reductions are hydrogenations and metal-mediated reactions such as,for example, tin(II) chloride, iron powder, zinc powder and compoundssimilar to these.

Hydrogenations can be carried out in a suitable solvent in the presenceof a catalyst under an atmosphere of hydrogen (standard pressure orelevated pressure). Suitable for use as catalysts are palladiumcatalysts such as, for example, palladium on carbon, nickel catalystssuch as Raney nickel, cobalt catalysts, ruthenium catalysts, rhodiumcatalysts, platinum catalysts and compounds similar to these. Suitablesolvents are water, alcohols such as methanol and ethanol, aromatichydrocarbons such as benzene and toluene, open-chain or cyclic etherssuch as diethyl ether, dioxane and tetrahydrofuran, and also esters suchas ethyl acetate. The reductions can be carried out in a pressure rangeof from 1 bar to 100 bar, where the temperature may vary between −20° C.and the boiling point of the solvent used. Depending on the reactionconditions, the reaction times are between a few minutes and 96 hours.

The metal-mediated reductions, for example with tin(II) chloride, can becarried out according to a process described in Organic Syntheses Coll.Vol. (III), 453.

Furthermore, (hetero)aromatic aminocarboxylic acids of the generalstructure (II-1-1) can also be prepared from the corresponding methylprecursors of type (X) by oxidation. Oxidizing agents suitable for suchoxidations are, for example, potassium permanganate, sodium dichromate,chromium trioxide and compounds similar to these [Tetrahedron Letters1995, 36(25), 4369-72; Bioorganic & Medicinal Chemistry Letters 2007,17(4), 1043-1046]. It is also possible to employ enzymatic processes forsuch oxidations [PCT Int. Appl., 9502061]. The reduction of the nitrofunction subsequently required can be carried out analogously to theprocess described above.

A further method for preparing (hetero)aromatic aminocarboxylic acids ofthe general structure (II-1-1) is the nitration of carboxylic acidprecursors represented by formula (XI) or (XII) and the subsequentreduction of the nitro function. The nitrations can be carried out usingprocesses known from the literature [Justus Liebigs Annalen der Chemie1958, 611, 194-205; Organikum, Wiley-VCH, 22. Edition, 358ff]. Thereduction of the nitro function subsequently required can be carried outanalogously to the process described above.

Furthermore, (hetero)aromatic aminocarboxylic acids of the generalstructure (II-1-1) can be prepared from the corresponding (hetero)aryltriflates of type (XIII) using a palladium-catalyzed process [Synthesis2006, (4), 594-596].

Compounds of the general formula (II-1) can be prepared from compoundsof the general formula (II-1-1) by established synthesis processes. Apossible synthesis route for the cyclic aminocarboxylic acids of thegeneral formula (II-1) is shown in Reaction Scheme 6.

The radicals A₁-A₄ have the meanings described above. The radical R¹represents the radicals described above except for hydrogen.

The conversion, known from the literature, of (II-1-1) into (II-1) cantake place inter alia via reductive amination [Bioorganic & MedicinalChemistry Letters 2005, 15(21), 4752-4756; WO2010-142402;US2010-0324056] or direct alkylation [Tetrahedron Letters 1977, (9),771-774; Journal of the American Chemical Society 1997, 119(9),2315-2316; Journal of Combinatorial Chemistry 2006, 8(6), 834-840].

Compounds of the general formula (II-2) can be prepared from compoundsof the general formula (II-1) by established synthesis processes. Apossible synthesis route for the cyclic aminocarboxylic acids of thegeneral formula (II-2) is shown in Reaction Scheme 7.

The radicals A₁-A₄ and R¹ have the meanings described above.

The conversion of compounds of the general formula (II-1) into compoundsof the general formula (II-2) can be carried out analogously toreactions known from the literature [US2009-0023798; WO2009-044200;WO2010-085352].

Possible syntheses for the heterocyclic carboxylic acid derivatives ofthe general formula (V) are shown in Reaction Scheme 8.

The radical W has the meanings described above. Hal represents asuitable halogen, for example bromine or iodine. X represents a suitableleaving group such as, for example, chlorine. T represents the grouping

where the radicals Z¹, Z² and Z³ have the meaning given above and theasterisk represents the point of attachment to the groupings Me, H, Hal,COOH, C(═S)OH or C(═W)X.

Heterocyclic carboxylic acids of the general structure (V-1) can beprepared inter alia from methyl derivatives of the general formula (XV)by oxidation of the methyl function. To this end, it is possible toemploy the processes already mentioned for the oxidation of methylgroups of the compounds of the general structure (X).

Heterocyclic carboxylic acids of the general structure (V-1) can beprepared from precursors of the general structure (XVI) by deprotonationusing a suitable base and by scavenging the corresponding carbanion withcarbon dioxide [Journal of Medicinal Chemistry 2008, 51(4), 937-947;Bioorganic & Medicinal Chemistry Letters 2007, 17(22), 6274-6279].Suitable bases are, for example, lithium diisopropylamide,n-butyllithium, s-butyllithium and compounds similar to these.

Also suitable for the process described above for preparing heterocycliccarboxylic acids of the general structure (V-1) are the appropriatelyhalogenated heterocycles (XVII). However, here the carbanion is notgenerated by deprotonation but by a metallation reaction [AngewandteChemie, International Edition 2008, 47(2), 311-315]. Preferred for thesemetallation reactions are n-butyllithium, t-butyllithium andisopropylmagnesium chloride.

Heterocyclic carboxylic acids of the general structure (V-1) can also beconverted from halogenated precursors of the general structure (XVII)with the aid of palladium-catalyzed reactions known from the literatureinto the corresponding heterocyclic carboxylic esters [Russian Journalof Applied Chemistry 2007, 80(4), 571-575].

Heterocyclic carboxylic acids of the general structure (V-1) canfurthermore be prepared from halogenated compounds of the generalstructure (XVII) by a substitution reaction of the halogens withcyanides and subsequent hydrolysis of the nitrile function with strongacid or bases [WO 2005079801].

Heterocyclic thiocarboxylic acids of the general structure (V-2) can beprepared from (V-1) analogously to the methods, known from theliterature, described for the preparation of compounds of the generalformula (II-2).

Heterocyclic activated carboxylic acid derivatives such as, for example,carbonyl halides as represented by the general structure (V) can beprepared by reacting a cyclic (thio)carboxylic acid represented by theformulae (V-1) and (V-2) with halogenating agents such as thionylchloride, thionyl bromide, phosphoryl chloride, oxalyl chloride,phosphorus trichloride etc. [Organikum, Wiley-VCH, 22. Edition, 496ff].

Activated carboxylic acid derivatives of the general structure (II) canbe prepared by generally known literature processes from carboxylicacids of the formula (II-1) [Organikum, Wiley-VCH, 22. Edition, 496ff;Chem. Ber. 1970, 788; J. Am. Chem. Soc 1967, 5012]. The compounds of theformula (II-1) are commercially available or can be prepared by knownliterature processes [Synthesis 2006, (4), 594-596; Tetrahedron Letters1995, 36(25), 4369-72; Bioorganic & Medicinal Chemistry Letters 2007,17(4), 1043-1046; PCT Int. Appl., 9502061, Journal of Organic Chemistry1954, 19, 357-64; WO 2001083459].

Compounds of the general structures (III) are commercially availableand/or can be prepared by the following processes, which are known fromthe literature or analogous [Journal of Organic Chemistry 1990, 55(14),4276-81; WO 2005028429; WO 2005021485; Organic Letters 2010, 12(9),1944-1947; Tetrahedron 1999, 55(24), 7625-7644].

Compounds of the general structure (V) are generally commerciallyavailable and/or can be prepared by known literature processes [Journalof Medicinal Chemistry 2008, 51(4), 937-947; Bioorganic & MedicinalChemistry Letters 2007, 17(22), 6274-6279; Russian Journal of AppliedChemistry 2007, 80(4), 571-575; WO 2005079801; Journal of OrganicChemistry 2008, 73(9), 3523-3529; Bioorganic & Medicinal ChemistryLetters 2005, 15(22), 4898-4906; US2006069270]

The compounds of the general structure (VI) can be prepared by processesknown from the literature from the compounds of the general structure(II) [Journal of the American Chemical Society 2001, 123(34), 8177-8188;Inorganica Chimica Acta 2006, 359(6), 1912-1922].

Compounds of the general structures (IX) to (XVII) are commerciallyavailable and/or known from the relevant specialist literature.

Oxidizing agents for the oxidation of alcoholic groups are known (cf.,for example, oxidizing agents in Organic Synthesis by Oxidation withMetal Compounds, Mijs, de Jonge, Plenum Verlag, New York, 1986;Manganese Compounds as Oxidizing Agens in Organic Chemistry, Arndt, OpenCourt Publishing Company, La Salle, Ill., 1981; The Oxidation of OrganicCompounds by Permanganate Ion and Hexavalent Chromium, Lee, Open CourtPublishing Company, La Salle, Ill., 1980). An oxidation can be carriedout, for example, in the presence of permanganates (for examplepotassium permanganate), metal oxides (for example manganese dioxide,chromium oxides which are used, for example, in dipyridinechromium(VI)oxide as Collins reagent (cf. J. C. Collins et al., Tetrahedron Lett.30, 3363-3366, 1968)). Likewise in the presence of pyridiniumchlorochromate (for example Corey's reagent) (cf. also R. O. Hutchins etal., Tetrahedron Lett. 48, 4167-4170, 1977; D. Landini et al. Synthesis134-136, 1979) or ruthenium tetroxide (cf. S.-I. Murahashi, N. KomiyaRuthenium-catalyzed Oxidation of Alkenes, Alcohols, Amines, Amides,β-Lactams, Phenols and Hydrocarbons, in: Modern Oxidation Methods,Baeckvall, Jan-Erling (Eds.), Wiley-VCH-Verlag GmbH & Co. KGaA, 2004).Likewise suitable are ultrasound-induced oxidation reactions and the useof potassium permanganate (cf. J. Yamawaki et al., Chem. Lett. 3,379-380, 1983).

All known suitable acidic or basic reaction auxiliaries can be usedaccording to the procedures described in the literature todeblock/remove the protective group SG. When protective groups of thecarbamate type are used for amino groups, preference is given to usingacidic reaction auxiliaries. When the t-butylcarbamate protective group(BOC group) is employed, for example, mixtures of mineral acids such ashydrochloric acid, hydrobromic acid, nitric acid, sulphuric acid,phosphoric acid or organic acids such as benzoic acid, formic acid,acetic acid, trifluoroacetic acid, methanesulphonic acid,benzenesulphonic acid or toluenesulphonic acid and a suitable diluentsuch as water and/or an organic solvent such as tetrahydrofuran,dioxane, dichloromethane, chloroform, ethyl acetate, ethanol or methanolare used. Preference is given to mixture of hydrochloric acid or aceticacid with water and/or an organic solvent such as ethyl acetate.

It is known that certain reactions and preparation processes can becarried out particularly efficiently in the presence of diluents orsolvents and basic or acidic reaction auxiliaries. It is also possibleto use mixtures of the diluents or solvents. The diluents or solventsare advantageously employed in such an amount that the reaction mixtureremains readily stirrable during the entire process.

Suitable diluents or solvents for carrying out the processes accordingto the invention are, in principle, all organic solvents which are inertunder the specific reaction conditions. Examples include:halohydrocarbons (for example chlorohydrocarbons such astetrachloroethylene, tetrachloroethane, dichloropropane, methylenechloride, dichlorobutane, chloroform, carbon tetrachloride,trichloroethane, trichloroethylene, pentachloroethane, difluorobenzene,1,2-dichloroethane, chlorobenzene, bromobenzene, dichlorobenzene,chlorotoluene, trichlorobenzene), alcohols (for example methanol,ethanol, isopropanol, butanol), ethers (for example ethyl propyl ether,methyl tert-butyl ether, n-butyl ether, anisole, phenetole, cyclohexylmethyl ether, dimethyl ether, diethyl ether, dipropyl ether, diisopropylether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethyleneglycol dimethyl ether, tetrahydrofuran, dioxane, dichlorodiethyl etherand polyethers of ethylene oxide and/or propylene oxide), amines (forexample trimethyl-, triethyl-, tripropyl-, tributylamine,N-methylmorpholine, pyridine and tetramethylenediamine),nitrohydrocarbons (for example nitromethane, nitroethane, nitropropane,nitrobenzene, chloronitrobenzene, o-nitrotoluene); nitriles (for exampleacetonitrile, propionitrile, butyronitrile, isobutyronitrile,benzonitrile, m-chlorobenzonitrile), tetrahydrothiophene dioxide,dimethyl sulphoxide, tetramethylene sulphoxide, dipropyl sulphoxide,benzyl methyl sulphoxide, diisobutyl sulphoxide, dibutyl sulphoxide,diisoamyl sulphoxide, sulphones (for example dimethyl, diethyl,dipropyl, dibutyl, diphenyl, dihexyl, methyl ethyl, ethyl propyl, ethylisobutyl and pentamethylene sulphone), aliphatic, cycloaliphatic oraromatic hydrocarbons (for example pentane, hexane, heptane, octane,nonane and technical hydrocarbons), and also what are called “whitespirits” with components having boiling points in the range from, forexample, 40° C. to 250° C., cymene, petroleum fractions within a boilingrange from 70° C. to 190° C., cyclohexane, methylcyclohexane, petroleumether, ligroin, octane, benzene, toluene, chlorobenzene, bromobenzene,nitrobenzene, xylene, esters (for example methyl, ethyl, butyl andisobutyl acetate, dimethyl, dibutyl and ethylene carbonate); amides (forexample hexamethylphosphoric triamide, formamide, N-methylformamide,N,N-dimethylformamide, N,N-dipropylformamide, N,N-dibutylformamide,N-methylpyrrolidine, N-methylcaprolactam,1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidine, octylpyrrolidone,octylcaprolactam, 1,3-dimethyl-2-imidazolinedione, N-formylpiperidine,N,N′-diformylpiperazine) and ketones (for example acetone, acetophenone,methyl ethyl ketone, methyl butyl ketone).

The basic reaction auxiliaries used to perform the process according tothe invention may be all suitable acid binders. Examples include:alkaline earth metal or alkali metal compounds (e.g. hydroxides,hydrides, oxides and carbonates of lithium, sodium, potassium,magnesium, calcium and barium), amidine bases or guanidine bases (e.g.7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD);diazabicyclo[4.3.0]nonene (DBN), diazabicyclo[2.2.2]octane (DABCO),1,8-diazabicyclo[5.4.0]undecene (DBU), cyclohexyltetrabutylguanidine(CyTBG), cyclohexyltetramethylguanidine (CyTMG),N,N,N,N-tetramethyl-1,8-naphthalenediamine, pentamethylpiperidine) andamines, especially tertiary amines (e.g. triethylamine, trimethylamine,tribenzylamine, triisopropylamine, tributylamine, tricyclohexylamine,triamylamine, trihexylamine, N,N-dimethylaniline, N,N-dimethyltoluidine,N,N-dimethyl-p-aminopyridine, N-methylpyrrolidine, N-methylpiperidine,N-methylimidazole, N-methylpyrazole, N-methylmorpholine,N-methylhexamethylenediamine, pyridine, 4-pyrrolidinopyridine,4-dimethylaminopyridine, quinoline, α-picoline, β-picoline,isoquinoline, pyrimidine, acridine, N,N,N′,N′-tetramethylenediamine,N,N,N′,N′-tetraethylenediamine, quinoxaline, N-propyldiisopropylamine,N-ethyldiisopropylamine, N,N′-dimethylcyclohexylamine, 2,6-lutidine,2,4-lutidine or triethyldiamine).

The acidic reaction auxiliaries used to perform the process according tothe invention include all mineral acids (e.g. hydrohalic acids such ashydrofluoric acid, hydrochloric acid, hydrobromic acid or hydriodicacid, and also sulphuric acid, phosphoric acid, phosphorous acid, nitricacid), Lewis acids (e.g. aluminium(III) chloride, boron trifluoride orits etherate, titanium(IV) chloride, tin(IV) chloride) and organic acids(e.g. formic acid, acetic acid, propionic acid, malonic acid, lacticacid, oxalic acid, fumaric acid, adipic acid, stearic acid, tartaricacid, oleic acid, methanesulphonic acid, benzoic acid, benzenesulphonicacid or para-toluenesulphonic acid).

If protective groups are intended in the reactions schemes, allgenerally known protective groups may be used. In particular thosedescribed by Greene T. W., Wuts P. G. W. in Protective Groups in OrganicSynthesis; John Wiley & Sons, Inc. 1999, “Protection for the hydroxylgroup including 1,2- and 1,3-diols”.

Also suitable are protective groups

of the substituted methyl ether type (for example methoxymethyl ether(MOM), methylthiomethyl ether (MTM), (phenyldimethylsilyl)methoxymethylether (SNOM-OR), benzyloxymethyl ether (BOM-OR)para-methoxybenzyloxymethyl ether (PMBM-OR), para-nitrobenzyloxymethylether, ortho-nitrobenzyloxymethyl ether (NBOM-OR),(4-methoxyphenoxy)methyl ether (p-AOM-OR), guaiacolmethyl ether(GUM-OR), t-butoxymethyl ether, 4-pentyloxymethyl ether (POM-OR),silyloxymethyl ether, 2-methoxyethoxymethyl ether (MEM-OR),2,2,2-trichloroethoxymethyl ether, bis(2-chloroethoxy)methyl ether,2-(trimethylsilyl)ethoxymethyl ether (SEM-OR), methoxymethyl ether(MM-OR));of the substituted ethyl ether type (for example 1-ethoxyethyl ether(EE-OR), 1-(2-chloroethoxy)ethyl ether (CEE-OR),1-[2-(trimethylsilyl)ethoxy]ethyl ether (SEE-OR),1-methyl-1-methoxyethyl ether (MIP-OR), 1-methyl-1-benzyloxyethyl ether(MBE-OR), 1-methyl-1-benzyloxy-2-fluoroethyl ether (MIP-OR),1-methyl-1-phenoxyethyl ether, 2,2,2-trichloroethyl ether,1,1-dianisyl-2,2,2-trichloroethyl ether (DATE-OR),1,1,1,3,3,3-hexafluoro-2-phenylisopropyl ether (HIP-OR),2-trimethylsilylethyl ether, 2-(benzylthio)ethyl ether,2-(phenylselenyl)ethyl ether), an ether (for example tetrahydropyranylether (THP-OR), 3-bromotetrahydropyranyl ether (3-BrTHP-OR),tetrahydrothiopyranyl ether, 1-methoxycyclohexyl ether, 2- and 4-picolylether, 3-methyl-2-picolyl-N-oxido ether, 2-quinolinylmethyl ether(Qm-OR), 1-pyrenylmethyl ether, diphenylmethyl ether (DPM-OR),para,para′-dinitrobenzhydryl ether (DNB-OR), 5-dibenzosuberyl ether,triphenylmethyl ether (Tr-OR), alpha-naphthyldiphenylmethyl ether,para-methoxyphenyldiphenylmethyl ether (MMTrOR),di(para-methoxyphenyl)phenylmethyl ether (DMTr-OR),tri(para-methoxyphenyl)phenylmethyl ether (TMTr-OR),4-(4′-bromophenacyloxy)phenyldiphenylmethyl ether,4,4′,4″-tris(4,5-dichlorophthalimidophenyl)methyl ether (CPTr-OR),4,4′,4″-tris(benzoyloxyphenyl)methyl ether (TBTr-OR),4,4′-dimethoxy-3″-[N-(imidazolylmethyl)]trityl ether (IDTr-OR),4,4′-dimethoxy-3″-[N-(imidazolyl-ethyl)carbamoyl]trityl ether (IETr-OR),1,1-bis(4-methoxyphenyl)-1′-pyrenylmethyl ether (Bmpm-OR), 9-anthrylether, 9-(9-phenyl)xanthenyl ether (Pixyl-OR),9-(9-phenyl-10-oxo)anthryl (tritylone ether), 4-methoxytetrahydropyranylether (MTHP-OR), 4-methoxytetrahydrothiopyranyl ether,4-methoxytetrahydrothiopyranyl S,S-dioxide,1-[(2-chloro-4-methyl)phenyl]-4-methoxypiperidin-4-yl ether (CTMP-OR),1-(2-fluorophenyl)-4-methoxypiperidin-4-yl ether (Fpmp-OR),1,4-dioxan-2-yl ether, tetrahydrofuranyl ether, tetrahydrothiofuranylether,2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanebenzofuran-2-ylether (MBF-OR), t-butyl ether, allyl ether, propargyl ether,para-chlorophenyl ether, para-methoxyphenyl ether, para-nitrophenylether, para-2,4-dinitrophenyl ether (DNP—OR),2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl ether, benzyl ether(Bn-OR));of the substituted benzyl ether type (for example para-methoxybenzylether (MPM-OR), 3,4-dimethoxybenzyl ether (DMPM-OR), ortho-nitrobenzylether, para-nitrobenzyl ether, para-halobenzyl ether, 2,6-dichlorobenzylether, para-aminoacylbenzyl ether (PAB-OR), para-azidobenzyl ether(Azb-OR), 4-azido-3-chlorobenzyl ether, 2-trifluoromethylbenzyl ether,para-(methylsulphinyl)benzyl ether (Msib-OR));of a silyl ether type (for example trimethylsilyl ether (TMS-OR),triethylsilyl ether (TES-OR), triisopropylsilyl ether (TIPS-OR),dimethylisopropylsilyl ether (IPDMS-OR), diethylisopropylsilyl ether(DEIPS-OR), dimethylhexylsilyl ether (TDS-OR), t-butyldimethylsilylether (TBDMS-OR), t-butyldiphenylsilyl ether (TBDPS-OR), tribenzylsilylether, tri-para-xylylsilyl ether, triphenylsilyl ether (TPS-OR),diphenylmethylsilyl ether (DPMS-OR), di-t-butylmethylsilyl ether(DTBMS-OR), tris(trimethylsilyl)silyl ether (sisyl ether),di-t-butylmethylsilyl ether (DTBMS-OR), tris(trimethylsilyl)silyl ether(sisyl ether), (2-hydroxystyryl)dimethylsilyl ether (HSDMS-OR),(2-hydroxystyryl)diisopropylsilyl ether (HSDIS-OR),t-butylmethoxyphenylsilyl ether (TBMPS-OR), t-butoxydiphenylsilyl ether(DPTBOS-OR));of the ester type (for example formate ester, benzoylformate ester,acetate ester (Ac-OR), chloroacetate ester, dichloroacetate ester,trichloroacetate ester, trifluoroacetate ester, (TFA-OR), methoxyacetateester, triphenylmethoxyacetate ester, phenoxyacetate ester,para-chlorophenoxyacetate ester, phenylacetate ester, diphenylacetateester (DPA-OR), nicotinate ester, 3-phenylpropionate ester, 4-pentoateester, 4-oxopentoate ester (levulinate) (Lev-OR)4,4-(ethylenedithio)pentanoate ester (LevS-OR),5-[3-bis(4-methoxyphenyl)hydroxymethoxyphenoxy]levulinate ester,pivaloate ester (Pv-OR), 1-adamantanoate ester, crotonate ester,4-methoxycrotonate ester, benzoate ester (Bz-OR), para-phenylbenzoateester, 2,4,6-trimethylbenzoate ester (mesitoate),4-(methylthiomethoxy)butyrate ester (MTMB-OR),2-(methylthiomethoxymethyl)benzoate ester (MTMT-OR),of the ester type (for example methyl carbonate, methoxymethylcarbonate, 9-fluorenylmethyl carbonate (Fmoc-OR), ethyl carbonate,2,2,2-trichloroethyl carbonate (Troc-OR),1,1-dimethyl-2,2,2-trichloroethyl carbonate (TCBOC-OR),2-(trimethylsilyl)ethyl carbonate (TMS-OR), 2-(phenylsulphonyl)ethylcarbonate (Ps-OR), 2-(triphenylphosphonio)ethyl carbonate (Peoc-OR),t-butyl carbonate (Boc-OR), isobutyl carbonate, vinyl carbonate, allylcarbonate (Alloc-OR), para-nitrophenyl carbonate, benzyl carbonate(Z-OR), para-methoxybenzyl carbonate, 3,4-dimethoxybenzyl carbonate,ortho-nitrobenzyl carbonate, para-nitrobenzyl carbonate, 2-dansylethylcarbonate (Dnseoc-OR), 2-(4-nitrophenyl)ethyl carbonate (Npeoc-OR),2-(2,4-dinitrophenyl)ethyl carbonate (Dnpeoc)), andof the sulphate type (for example allylsulphonate (Als-OR),methanesulphonate (Ms-OR), benzylsulphonate, tosylate (Ts-OR),2-[(4-nitrophenyl)ethyl]sulphonate (Npes-OR)).

Suitable catalysts for carrying out a catalytic hydrogenation in theprocess according to the invention are all customary hydrogenationcatalysts such as, for example, platinum catalysts (for example platinumplate, platinum sponge, platinum black, colloidal platinum, platinumoxide, platinum wire), palladium catalysts (for example palladiumsponge, palladium black, palladium oxide, palladium/carbon, colloidalpalladium, palladium/barium sulphate, palladium/barium carbonate,palladium hydroxide, nickel catalysts (for example reduced nickel,nickel oxide, Raney nickel), ruthenium catalysts, cobalt catalysts (forexample reduced cobalt, Raney cobalt), copper catalysts (for examplereduced copper, Raney copper, Ullmann copper). Preference is given tousing noble metal catalysts (for example platinum and palladium orruthenium catalysts), which may be applied to a suitable support (forexample carbon or silicon), rhodium catalysts (for exampletris(triphenylphosphine)rhodium(I) chloride in the presence oftriphenylphosphine). Furthermore, it is possible to use “chiralhydrogenation catalysts” (for example those comprising chiraldiphosphine ligands such as (2S,3S)-(−)-2,3-bis(diphenylphosphino)butane[(S,S)-chiraphos] or (R)-(+)-2,2′- or(S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene [R(+)-BINAP orS(−)-BINAP]), whereby the proportion of an isomer in the isomer mixtureis increased or the formation of another isomer is virtually completelysuppressed.

Salts of the compounds according to the invention are prepared bystandard methods. Representative acid addition salts are, for example,those formed by reaction with inorganic acids, such as, for example,sulphuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, ororganic carboxylic acids such as acetic acid, trifluoroacetic acid,citric acid, succinic acid, butyric acid, lactic acid, formic acid,fumaric acid, maleic acid, malonic acid, camphoric acid, oxalic acid,phthalic acid, propionic acid, glycolic acid, glutaric acid, stearicacid, salicylic acid, sorbic acid, tartaric acid, cinnamic acid, valericacid, picric acid, benzoic acid or organic sulphonic acids such asmethanesulphonic acid and 4-toluenesulphonic acid.

Also representative are salts of compounds according to the inventionformed from organic bases such as, for example, pyridine ortriethylamine, or those formed from inorganic bases such as, forexample, hydrides, hydroxides or carbonates of sodium, lithium, calcium,magnesium or barium, provided the compounds of the general formula (I)have a structural element suitable for this salt formation.

Synthesis methods for preparing heterocyclic N-oxides and t-amines areknown. They can be obtained using peroxy acids (for example peraceticacid and meta-chloroperbenzoic acid (MCPBA), hydrogen peroxide), alkylhydroperoxides (for example t-butyl hydroperoxide), sodium perborate anddioxiranes (for example dimethyldioxirane). These methods have beendescribed, for example, by T. L. Gilchrist, in Comprehensive OrganicSynthesis, Vol. 7, pp. 748-750, 1992, S. V. Ley, (Ed.), Pergamon Press;M. Tisler, B. Stanovnik, in Comprehensive Heterocyclic Chemistry, Vol.3, pp. 18-20, 1984, A. J. Boulton, A. McKillop, (Eds.), Pergamon Press;M. R. Grimmett, B. R. T. Keene in Advances in Heterocyclic Chemistry,Vol. 43, pp. 149-163, 1988, A. R. Katritzky, (Ed.), Academic Press; M.Tisler, B. Stanovnik, in Advances in Heterocyclic Chemistry, Vol. 9, pp.285-291, 1968, A. R. Katritzky, A. J. Boulton (Eds.), Academic Press; G.W. H. Cheeseman, E. S. G. Werstiuk in Advances in HeterocyclicChemistry, Vol. 22, pp. 390-392, 1978, A. R. Katritzky, A. J. Boulton,(Eds.), Academic Press.

EXPERIMENTAL PART Preparation Process A Example (1)4-Bromo-N-{4-chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl}-3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxamide

120 mg (0.45 mmol) of4-bromo-3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylic acidare suspended in 20 ml of dichloromethane p.a., and 0.02 ml ofN,N-dimethylformamide p.a. is added. 0.119 ml (1.36 mmol) of oxalylchloride is added dropwise to this mixture. The mixture is then stirredat room temperature for 30 minutes and then under reflux for 30 minutes.After cooling, the reaction mixture is concentrated under reducedpressure on a rotary evaporator. The crude product obtained in this wayis reacted further without further purification.

108 mg (0.45 mmol) of 5-amino-2-chloro-N-(1-cyanocyclopropyl)benzamideand 92 mg (0.68 mmol) of silver(I) cyanide are initially charged in 10ml of dichlormethane p.a. A solution of 129 mg (0.45 mmol) of4-bromo-3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carbonyl chloridein 10 ml of dichloromethane p.a. is added dropwise to this suspension.The reaction mixture is stirred at room temperature for 16 h and thenfiltered through silica gel, and the filter cake is washed with ethylacetate. The solvents are removed under reduced pressure on a rotaryevaporator.

This gives 170 mg (78%) of4-bromo-N-{4-chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl}-3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxamideas a colourless solid.

¹H-NMR (400 MHz, d₆-DMSO): δ=10.96 (s, 1H), 9.49 (s, 1H), 7.85 (d, 1H),7.74 (dd, 1H), 7.55 (d, 1H), 3.93 (s, 3H), 1.57-1.61 (m, 2H), 1.40-1.45(m, 2H), 1.23-1.28 (m, 2H), 1.08-1.11 (m, 2H) ppm.

HPLC-MS^(a)): log P=2.50, mass (m/z)=482 [M+H]⁺.

Preparation Process B Example (2)N-{4-Chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl}-N,1-dimethyl-3,4-bis(trifluoromethyl)-1H-pyrazole-5-carboxamide

150.0 mg (0.29 mmol) of2-chloro-5-(methyl{[1-methyl-3,4-bis(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzoicacid are suspended in 5.0 ml of dichlormethane p.a. 0.02 ml ofN,N-dimethylformamide p.a. and 0.075 ml (0.86 mmol) oxalyl chloride arethen added successively to the suspension. The reaction mixture isstirred at room temperature for 0.5 h and then heated under reflux for40 minutes. The solvent is removed under reduced pressure on a rotaryevaporator. The2-chloro-5-(methyl{[1-methyl-3,4-bis(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzoylchloride formed is used for the subsequent synthesis step withoutfurther purification.

68.3 mg (0.58 mmol) of 1-aminocyclopropanecarbonitrile hydrochloride areinitially charged in 5.0 ml of dichloromethane p.a., and 0.148 ml (0.86mmol) of N-ethyldiisopropylamine and 156 mg of2-chloro-5-(methyl{[1-methyl-3,4-bis(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzoylchloride (0.29 mmol) dissolved in 5.0 ml of dichloromethane p.a. arethen added in succession. The reaction is stirred at room temperaturefor 16 hours. The reaction solution is diluted with 30 ml of ethylacetate. The organic phase is washed twice with 1 N hydrochloric acid,once with 1 N aqueous sodium hydroxide solution and once with saturatedsodium chloride solution. The organic phase is dried over magnesiumsulphate and filtered and the solvent is removed on a rotary evaporatorunder reduced pressure.

The crude product is purified by preparative HPLC. This gives 64 mg(45%) ofN-{4-chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl}-N,1-dimethyl-3,4-bis(trifluoromethyl)-1H-pyrazole-5-carboxamideas a colourless solid.

¹H-NMR (400 MHz, d₃-acetonitrile, mixture of cis- and trans-configuredamides): δ=7.42-7.66 (m, 2H), 7.40 (d, 1H), 7.29 (d, 2H), 7.18 (dd, 1H),3.83 & 3.99 (2 s, together 3H), 3.46 & 3.23 (2 s, together 3H),1.54-1.60 (m, 2H), 1.25-1.37 (m, 2H) ppm.

HPLC-MS^(a)): log P=2.81, mass (m/z)=494 [M+H]⁺.

Preparation Process C Example (50)N-{4-Chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl}-N-ethyl-3-(pentafluoroethyl)-1-propyl-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide

70 mg (0.13 mmol) ofN-{4-chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl}-3-(pentafluoroethyl)-1-propyl-4-(trifluoromethyl)-1H-pyrazole-5-carboxamideand 35 mg (0.14 mmol) of potassium carbonate are suspended in 1.4 ml ofN,N-dimethylformamide p.a. Over a period of 16 h, a total of 29 mg (0.19mmol) of iodoethane are added gradually to the mixture. After theaddition has ended, the reaction solution is stirred at room temperaturefor 20 h. The reaction mixture is diluted with water, and the aqueousphase is extracted three times with ethyl acetate. The combined organicphases are washed twice with saturated sodium chloride solution, driedover sodium sulphate and filtered. The solvents are removed on a rotaryevaporator under reduced pressure.

The crude product is purified by column chromatography on silica gel.This gives 30 mg (41%) ofN-{4-chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl}-N-ethyl-3-(pentafluoroethyl)-1-propyl-4-(trifluoromethyl)-1H-pyrazole-5-carboxamideas a colourless solid.

¹H-NMR (400 MHz, d₆-DMSO, mixture of cis- and trans-configured amides):δ=9.56 & 9.42 (2s, together 1H), 7.69 & 7.56 (2d, together 1H), 7.63 &7.42 (2d, together 1H), 7.48 & 7.28 (2dd, together 1H), 3.52-4.32 (m,4H), 0.79-1.87 (m, 12H) ppm.

HPLC-MS^(a)): log P=4.06, mass (m/z)=586 [M+H]⁺.

Preparation Process D Example (40)N-{3-[Acetyl(1-cyanocyclopropyl)carbamoyl]-4-chlorophenyl}-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide

300 mg (0.57 mmol) ofN-{4-chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl}-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamideare dissolved in 6.0 ml of dichloromethane p.a. and cooled in an icebath. 0.17 ml (0.99 mmol) of N-ethyldiisopropylamine and 49 mg (0.62mmol) of acetyl chloride are added successively to the solution. Thereaction is then warmed to room temperature and stirred for 16 h. Thereaction solution is diluted with dichloromethane and then washed withwater. The organic phase is dried over sodium sulphate and filtered, andthe solvent is removed on a rotary evaporator under reduced pressure.

The crude product is purified by preparative HPLC. This gives 130 mg(40%) ofN-{3-[acetyl(1-cyanocyclopropyl)carbamoyl]-4-chlorophenyl}-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamideas a colourless solid.

¹H-NMR (400 MHz, d₆-DMSO): δ=11.49 (s, 1H), 7.90 (d, 1H), 7.70 (dd, 1H),7.57 (d, 1H), 4.03 (s, 3H), 2.49 (s, 3H), 1.85-1.91 (m, 2H), 1.57-1.67(m, 2H) ppm.

HPLC-MS^(a)): log P=3.81, Masse (m/z)=572 [M+H]⁺.

^(a)) Note regarding the determination of the log P values and massdetection The determination of the given log P values was carried out inaccordance with EEC Directive 79/831 Annex V.A8 by HPLC (HighPerformance Liquid Chromatography) on a reversed-phase column (C18).Agilent 1100 LC system; 50*4.6 Zorbax Eclipse Plus C18 1.8 micron;mobile phase A: acetonitrile (0.1% formic acid); mobile phase B: water(0.09% formic acid); linear gradient from 10% acetonitrile to 95%acetonitrile in 4.25 min, then 95% acetonitrile for a further 1.25 min;oven temperature 55° C.; flow rate: 2.0 ml/min Mass detection is via anAgilend MSD system.

^(b)) Note regarding the determination of the log P values and massdetection The stated log P values were determined in accordance with EECDirective 79/831 Annex V.A8 by HPLC (High Performance LiquidChromatography) using a reversed-phase column (C18). HP1100; 50*4.6Zorbax Eclipse Plus C18 1.8 micron; mobile phase A: acetonitrile (0.1%formic acid); mobile phase B: water (0.08% formic acid); linear gradientfrom 5% acetonitrile to 95% acetonitrile in 1.70 min, then 95%acetonitrile for a further 1.00 min; oven temperature 55° C.; flow rate:2.0 ml/min Mass detection is via the mass detector Micromass ZQ2000 fromWaters.

The compounds listed in Tables 1 & 2 were prepared using the PreparationProcesses A to D described above.

TABLE 1 (I-1)

Mass Ex. No Z¹ Z² Z³ R¹ A¹ A² A³ A⁴ W R⁶ Q logP [m/z] 1 1 1-fluoro- BrMe H CH CH CCl CH O H 1-cyano- 2.50 ^(a)) 482 ^(a)) cyclopropylcyclopropyl 2 CF₃ CF₃ Me Me CH CH CCl CH O H 1-cyano- 2.81 ^(a)) 494^(a)) cyclopropyl 3 1-chloro- Cl Me Me CH CH CCl CH O H 1-cyano- 2.46^(a)) 466 ^(a)) cyclopropyl cyclopropyl 4 penta- CF₃ Me Me CH CH CCl CHO Et 1-cyano- 3.77 ^(a)) 572 ^(a)) fluoroethyl cyclopropyl 5 penta- CF₃Me Me CH CH CCl CH O Me 1-cyano- 3.59 ^(a)) 558 ^(a)) fluoroethylcyclopropyl 6 penta- CF₃ Me Et CH CH CCl CH O H 1-cyano- 3.36 ^(a)) 558^(a)) fluoroethyl cyclopropyl 7 penta- CF₃ Me H CH CH CCl CH O H1-cyano- 3.55 ^(a)) 544 ^(a)) fluoroethyl cyclobutyl 8 penta- CF₃ Me MeCH CH CCl CH O H 1-cyano- 3.21 ^(a)) 544 ^(a)) fluoroethyl cyclopropyl 9CF₃ CF₃ Me H CH CH CCl CH O H 1-cyano- 2.85 ^(a)) 480 ^(a)) cyclopropyl10 penta- CF₃ Me H CH CH CCl CH O H 1-cyano- 3.27 ^(a)) 530 ^(a))fluoroethyl cyclopropyl 11 CF₃ CF₃ Me H CH CBr CBr CH O H 1-cyano- 3.30604 cyclopropyl 12 CF₃ CF₃ Me H CH CCl CBr CH O H 1-cyano- 3.27 560cyclopropyl 13 penta- CF₃ Me H CH CBr CCl CH O H 1-cyano- 3.67 610fluoroethyl cyclopropyl 14 penta- CF₃ Me H CH CH CBr CH O H 1 -cyano-3.31 576 fluoroethyl cyclopropyl 15 penta- CF₃ Me H CH CH CCl CH Opropionyl 1-cyano- 4.17 584 ² fluoroethyl cyclopropyl 16 penta- CF₃ Me HCH CCl CBr CH O H 1-cyano- 3.73 610 fluoroethyl cyclopropyl 17 1-fluoro-Cl Me H CH CH CCl CH O H 1-cyano- 2.50 436 cyclopropyl cyclopropyl 18penta- CF₃ Me acetyl CH CH CCl CH O acetyl 1-cyano- 4.04 fluoroethylcyclopropyl 19 penta- CF₃ Me methoxy- CH CH CCl CH O H 1-cyano- 3.69 588fluoroethyl carbonyl cyclopropyl 20 penta- CF₃ Me ethoxy- CH CH CCl CH OH 1-cyano- 3.95 602 fluoroethyl carbonyl cyclopropyl 21 penta- CF₃ Memethoxy- CH CH CCl CH O methoxy- 1-cyano- 4.32 646 fluoroethyl carbonylcarbonyl cyclopropyl 22 penta- CF₃ Me ethoxy- CH CH CCl CH O ethoxy-1-cyano- 4.80 674 fluoroethyl carbonyl carbonyl cyclopropyl 23 penta-CF₃ Me 2,2-dimethyl- CH CH CCl CH O H 1-cyano- 4.40 614 fluoroethylpropanoyl cyclopropyl 24 penta- CF₃ Me H CH CMe CCl CH O H 1-cyano- 3.51544 fluoroethyl cyclopropyl 25 penta- CF₃ Me H CH CH Cl CH O H 1-cyano-3.43 620 ² fluoroethyl cyclopropyl 26 penta- CF₃ Me prop-2- CH CH CCl CHO H 1-cyano- 3.41 568 fluoroethyl yn-1-yl cyclopropyl 27 penta- CF₃ Me HCH CH CF CH O H 1-cyano- 3.21 514 fluoroethyl cyclopropyl 28 penta- CF₃Me 4-chloro- CH CH CCl CH O H 1-cyano- 4.30 654 fluoroethyl benzylcyclopropyl 29 penta- CF₃ Me isobutyryl CH CH CCl CH O H 1-cyano- 4.38600 fluoroethyl cyclopropyl 30 penta- CF₃ Me but-2- CH CH CCl CH O H1-cyano- 3.60 582 fluoroethyl yn-1-yl cyclopropyl 31 penta- CF₃ Mebenzyl CH CH CCl CH O H 1-cyano- 3.97 620 fluoroethyl cyclopropyl 32penta- CF₃ Me pyridin-2- CH CH CCl CH O H 1-cyano- 3.53 621 fluoroethylylmethyl cyclopropyl 33 penta- CF₃ Me propionyl CH CH CCl CH O H1-cyano- 3.91 586 fluoroethyl cyclopropyl 34 penta- CF₃ Et H CH CH CClCH O H 1-cyano- 3.53 544 fluoroethyl cyclopropyl 35 penta- CF₃ Pr H CHCH CCl CH O H 1-cyano- 3.87 558 fluoroethyl cyclopropyl 36 penta- CF₃ PrH CH CH CF CH O H 1-cyano- 3.74 542 fluoroethyl cyclopropyl 37 penta-CF₃ Et H CH CH CF CH O H 1-cyano- 3.44 528 fluoroethyl cyclopropyl 38penta- CF₃ Et Me CH CH CCl CH O H 1-cyano- 3.57 558 fluoroethylcyclopropyl 39 penta- CF₃ Me Et CH CBr CCl CH O H 1-cyano- 3.92 638fluoroethyl cyclopropyl 40 penta- CF₃ Me H CH CH CCl CH O acetyl1-cyano- 3.81 572 fluoroethyl cyclopropyl 41 penta- CF₃ Et Me CH CH CClCH O Me 1-cyano- 3.85 572 fluoroethyl cyclopropyl 42 penta- methyl- Me HCH CH CCl CH O H 1-cyano- 3.43 508 fluoroethyl sulphanyl cyclopropyl 43penta- CF₃ Et Et CH CH CCl CH O H 1-cyano- 3.68 572 fluoroethylcyclopropyl 44 penta- CF₃ Me cyano- CH CH CCl CH O H 1-cyano- 3.25 569fluoroethyl methyl cyclopropyl 45 penta- methyl- Me H CH CH CCl CH O H1-cyano- 2.91 524 fluoroethyl sulphinyl cyclopropyl 46 penta- CF₃ Pr MeCH CH CCl CH O Me 1-cyano- 4.26 586 fluoroethyl cyclopropyl 47 penta-CF₃ Pr Me CH CH CF CH O Me 1-cyano- 4.05 570 fluoroethyl cyclopropyl 48penta- CF₃ Et Me CH CH CF CH O Me 1-cyano- 3.76 556 fluoroethylcyclopropyl 49 penta- methyl- Me H CH CH CCl CH O H 1-cyano- 2.47 540fluoroethyl sulphonyl cyclopropyl 50 penta- CF₃ Pr Et CH CH CCl CH O H1-cyano- 4.06 586 fluoroethyl cyclopropyl 51 penta- CF₃ Pr Et CH CH CClCH O Et 1-cyano- 4.68 614 fluoroethyl cyclopropyl 52 penta- CF₃ Et Et CHCH CCl CH O Et 1-cyano- 4.26 600 fluoroethyl cyclopropyl 53 penta- CF₃Me acetyl CH CH CCl CH O H 1-cyano- 3.63 572 fluoroethyl cyclopropyl 54penta- CF₃ Me pyridin-3- CH CH CCl CH O H 1-cyano- 2.85 621 fluoroethylylmethyl cyclopropyl 55 penta- CF₃ Me 2-methylprop- CH CH CCl CH O H1-cyano- 3.78 584 fluoroethyl 2-en-1-yl cyclopropyl 56 penta- CF₃ Mepyridin-4- CH CH CCl CH O H 1-cyano- 2.52 621 fluoroethyl ylmethylcyclopropyl 57 penta- CF₃ prop-2- H CH CH CCl CH O H 1-cyano- 3.58 554fluoroethyl yn-1-yl cyclopropyl 58 penta- CF₃ prop-2- H CH CH CCl CH O H1-cyano- 3.65 556 fluoroethyl en-1-yl cyclopropyl 59 penta- CF₃ Me H CHCF CBr CH O H 1-cyano- 3.58 592 fluoroethyl cyclopropyl 60 penta- CF₃ Mepropionyl CH CH CCl CH O propionyl 1-cyano- 4.68 fluoroethyl cyclopropyl61 penta- CF₃ Me H CH CH CCl CH O Et 1-cyano- 3.86 558 fluoroethylcyclopropyl 62 penta- CF₃ Me H CH CH CCl CH O Me 1-cyano- 3.66 544fluoroethyl cyclopropyl 63 penta- CF₃ Me isopropoxy- CH CH CCl CH O H1-cyano- 4.19 616 fluoroethyl carbonyl cyclopropyl 64 penta- CF₃2,2,2-tri- H CH CH CCl CH O H 1-cyano- 3.60 598 fluoroethyl fluoroethylcyclopropyl 65 CF₃ CF₃ Me H CH CH CCl CH S H 1-cyano- cyclopropyl 66penta- CF₃ Me Me CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 67penta- CF₃ Me H CH CH CCl CH S H 1-cyano- fluoroethyl cyclobutyl 68penta- CF₃ Me Et CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 69penta- CF₃ Me Me CH CH CCl CH S Me 1-cyano- fluoroethyl cyclopropyl 70penta- CF₃ Me Me CH CH CCl CH S Et 1-cyano- fluoroethyl cyclopropyl 711-chloro- Cl Me Me CH CH CCl CH S H 1-cyano- cyclopropyl cyclopropyl 72CF₃ CF₃ Me Me CH CH CCl CH S H 1-cyano- cyclopropyl 73 penta- CF₃ Me HCH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 74 1-fluoro- Br Me HCH CH CCl CH S H 1-cyano- cyclopropyl cyclopropyl 75 CF₃ CF₃ Me H CH CBrCBr CH S H 1-cyano- cyclopropyl 76 CF₃ CF₃ Me H CH CCl CBr CH S H1-cyano- cyclopropyl 77 penta- CF₃ Me H CH CBr CCl CH S H 1-cyano-fluoroethyl cyclopropyl 78 penta- CF₃ Me H CH CH CBr CH S H 1-cyano-fluoroethyl cyclopropyl 79 penta- CF₃ Me H CH CH CCl CH S propionyl1-cyano- fluoroethyl cyclopropyl 80 penta- CF₃ Me H CH CCl CBr CH S H1-cyano- fluoroethyl cyclopropyl 81 1-fluoro- Cl Me H CH CH CCl CH S H1-cyano- cyclopropyl cyclopropyl 82 penta- CF₃ Me acetyl CH CH CCl CH Sacetyl 1-cyano- fluoroethyl cyclopropyl 83 penta- CF₃ Me methoxy- CH CHCCl CH S H 1-cyano- fluoroethyl carbonyl cyclopropyl 84 penta- CF₃ Meethoxy- CH CH CCl CH S H 1-cyano- fluoroethyl carbonyl cyclopropyl 85penta- CF₃ Me methoxy- CH CH CCl CH S methoxy- 1-cyano- fluoroethylcarbonyl carbonyl cyclopropyl 86 penta- CF₃ Me ethoxy- CH CH CCl CH Sethoxy- 1-cyano- fluoroethyl carbonyl carbonyl cyclopropyl 87 penta- CF₃Me 2,2-dimethyl- CH CH CCl CH S H 1-cyano- fluoroethyl propanoylcyclopropyl 88 penta- CF₃ Me H CH CMe CCl CH S H 1-cyano- fluoroethylcyclopropyl 89 penta- CF₃ Me H CH CH Cl CH S H 1-cyano- fluoroethylcyclopropyl 90 penta- CF₃ Me prop-2- CH CH CCl CH S H 1-cyano-fluoroethyl yn-1-yl cyclopropyl 91 penta- CF₃ Me H CH CH CF CH S H1-cyano- fluoroethyl cyclopropyl 92 penta- CF₃ Me 4-chloro- CH CH CCl CHS H 1-cyano- fluoroethyl benzyl cyclopropyl 93 penta- CF₃ Me isobutyrylCH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 94 penta- CF₃ Mebut-2- CH CH CCl CH S H 1-cyano- fluoroethyl yn-1-yl cyclopropyl 95penta- CF₃ Me benzyl CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl96 penta- CF₃ Me pyridin-2- CH CH CCl CH S H 1-cyano- fluoroethylylmethyl cyclopropyl 97 penta- CF₃ Me propionyl CH CH CCl CH S H1-cyano- fluoroethyl cyclopropyl 98 penta- CF₃ Et H CH CH CCl CH S H1-cyano- fluoroethyl cyclopropyl 99 penta- CF₃ Pr H CH CH CCl CH S H1-cyano- fluoroethyl cyclopropyl 100 penta- CF₃ Pr H CH CH CF CH S H1-cyano- fluoroethyl cyclopropyl 101 penta- CF₃ Et H CH CH CF CH S H1-cyano- fluoroethyl cyclopropyl 102 penta- CF₃ Et Me CH CH CCl CH S H1-cyano- fluoroethyl cyclopropyl 103 penta- CF₃ Me Et CH CBr CCl CH S H1-cyano- fluoroethyl cyclopropyl 104 penta- CF₃ Me H CH CH CCl CH Sacetyl 1-cyano- fluoroethyl cyclopropyl 105 penta- CF₃ Et Me CH CH CClCH S Me 1-cyano- fluoroethyl cyclopropyl 106 penta- methyl- Me H CH CHCCl CH S H 1-cyano- fluoroethyl sulphanyl cyclopropyl 107 penta- CF₃ EtEt CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 108 penta- CF₃ Mecyano- CH CH CCl CH S H 1-cyano- fluoroethyl methyl cyclopropyl 109penta- methyl- Me H CH CH CCl CH S H 1-cyano- fluoroethyl sulphinylcyclopropyl 110 penta- CF₃ Pr Me CH CH CCl CH S Me 1-cyano- fluoroethylcyclopropyl 111 penta- CF₃ Pr Me CH CH CF CH S Me 1-cyano- fluoroethylcyclopropyl 112 penta- CF₃ Et Me CH CH CF CH S H 1-cyano- fluoroethylcyclopropyl 113 penta- methyl- Me H CH CH CCl CH S H 1-cyano-fluoroethyl sulphonyl cyclopropyl 114 penta- CF₃ Pr Et CH CH CCl CH S H1-cyano- fluoroethyl cyclopropyl 115 penta- CF₃ Pr Et CH CH CCl CH S Et1-cyano- fluoroethyl cyclopropyl 116 penta- CF₃ Et Et CH CH CCl CH S Et1-cyano- fluoroethyl cyclopropyl 117 penta- CF₃ Me acetyl CH CH CCl CH SH 1-cyano- fluoroethyl cyclopropyl 118 penta- CF₃ Me pyridin-3- CH CHCCl CH S H 1-cyano- fluoroethyl ylmethyl cyclopropyl 119 penta- CF₃ Me2-methylprop- CH CH CCl CH S H 1-cyano- fluoroethyl 2-en-1-ylcyclopropyl 120 penta- CF₃ Me pyridin-4- CH CH CCl CH S H 1-cyano-fluoroethyl ylmethyl cyclopropyl 121 penta- CF₃ prop-2- H CH CH CCl CH SH 1-cyano- fluoroethyl yn-1-yl cyclopropyl 122 penta- CF₃ prop-2- H CHCH CCl CH S H 1-cyano- fluoroethyl en-1-yl cyclopropyl 123 penta- CF₃ MeH CH CF CBr CH S H 1-cyano- fluoroethyl cyclopropyl 124 penta- CF₃ Mepropionyl CH CH CCl CH S propionyl 1-cyano- fluoroethyl cyclopropyl 125penta- CF₃ Me H CH CH CCl CH S Et 1-cyano- fluoroethyl cyclopropyl 126penta- CF₃ Me H CH CH CCl CH S Me 1-cyano- fluoroethyl cyclopropyl 127penta- CF₃ Me isopropoxy- CH CH CCl CH S H 1-cyano- fluoroethyl carbonylcyclopropyl 128 penta- CF₃ 2,2,2-tri- H CH CH CCl CH S H 1-cyano-fluoroethyl fluoroethyl cyclopropyl

TABLE 2 (Ib)

Mass Ex. No Z¹ Z² Z³ R¹ A¹ A² A³ A⁴ W R⁶ Q logP [m/z] 1 129 1-fluoro- BrMe H CH CH CCl CH O H 1-cyano- cyclopropyl cyclopropyl 130 CF₃ CF₃ Me MeCH CH CCl CH O H 1-cyano- cyclopropyl 131 1-chloro- Cl Me Me CH CH CClCH O H 1-cyano- cyclopropyl cyclopropyl 132 penta- CF₃ Me Me CH CH CClCH O Et 1-cyano- fluoroethyl cyclopropyl 133 penta- CF₃ Me Me CH CH CClCH O Me 1-cyano- fluoroethyl cyclopropyl 134 penta- CF₃ Me Et CH CH CClCH O H 1-cyano- fluoroethyl cyclopropyl 135 penta- CF₃ Me H CH CH CCl CHO H 1-cyano- fluoroethyl cyclobutyl 136 penta- CF₃ Me Me CH CH CCl CH OH 1-cyano- fluoroethyl cyclopropyl 137 CF₃ CF₃ Me H CH CH CCl CH O H1-cyano- cyclopropyl 138 penta- CF₃ Me H CH CH CCl CH O H 1-cyano-fluoroethyl cyclopropyl 139 CF₃ CF₃ Me H CH CBr CBr CH O H 1-cyano-cyclopropyl 140 CF₃ CF₃ Me H CH CCl CBr CH O H 1-cyano- cyclopropyl 141penta- CF₃ Me H CH CBr CCl CH O H 1-cyano- fluoroethyl cyclopropyl 142penta- CF₃ Me H CH CH CBr CH O H 1-cyano- fluoroethyl cyclopropyl 143penta- CF₃ Me H CH CH CCl CH O propionyl 1-cyano- fluoroethylcyclopropyl 144 penta- CF₃ Me H CH CCl CBr CH O H 1-cyano- fluoroethylcyclopropyl 145 1-fluoro- Cl Me H CH CH CCl CH O H 1-cyano- cyclopropylcyclopropyl 146 penta- CF₃ Me acetyl CH CH CCl CH O acetyl 1-cyano-fluoroethyl cyclopropyl 147 penta- CF₃ Me methoxy- CH CH CCl CH O H1-cyano- fluoroethyl carbonyl cyclopropyl 148 penta- CF₃ Me ethoxy- CHCH CCl CH O H 1-cyano- fluoroethyl carbonyl cyclopropyl 149 penta- CF₃Me methoxy- CH CH CCl CH O methoxy- 1-cyano- fluoroethyl carbonylcarbonyl cyclopropyl 150 penta- CF₃ Me ethoxy- CH CH CCl CH O ethoxy-1-cyano- fluoroethyl carbonyl carbonyl cyclopropyl 151 penta- CF₃ Me2,2-dimethyl- CH CH CCl CH O H 1-cyano- fluoroethyl propanoylcyclopropyl 152 penta- CF₃ Me H CH CMe CCl CH O H 1-cyano- fluoroethylcyclopropyl 153 penta- CF₃ Me H CH CH Cl CH O H 1-cyano- fluoroethylcyclopropyl 154 penta- CF₃ Me prop-2- CH CH CCl CH O H 1-cyanofluoroethyl yn-1-yl cyclopropyl 155 penta- CF₃ Me H CH CH CF CH O H1-cyano- fluoroethyl cyclopropyl 156 penta CF₃ Me 4-chloro- CH CH CCl CHO H 1-cyano- fluoroethyl benzyl cyclopropyl 157 penta- CF₃ Me isobutyrylCH CH CCl CH O H 1-cyano- fluoroethyl cyclopropyl 158 penta CF₃ Mebut-2- CH CH CCl CH O H 1-cyano- fluoroethyl yn-1-yl cyclopropyl 159penta- CF₃ Me benzyl CH CH CCl CH O H 1-cyano- fluoroethyl cyclopropyl160 penta- CF₃ Me pyridin-2- CH CH CCl CH O H 1-cyano- fluoroethylylmethyl cyclopropyl 161 penta- CF₃ Me propionyl CH CH CCl CH O H1-cyano- fluoroethyl cyclopropyl 162 penta- CF₃ Et H CH CH CCl CH O H1-cyano- fluoroethyl cyclopropyl 163 penta- CF₃ Pr H CH CH CCl CH O H1-cyano- fluoroethyl cyclopropyl 164 penta- CF₃ Pr H CH CH CF CH O H1-cyano- fluoroethyl cyclopropyl 165 penta- CF₃ Et H CH CH CF CH O H1-cyano- fluoroethyl cyclopropyl 166 penta- CF₃ Et Me CH CH CCl CH O H1-cyano- fluoroethyl cyclopropyl 167 penta- CF₃ Me Et CH CBr CCl CH O H1-cyano- fluoroethyl cyclopropyl 168 penta- CF₃ Me H CH CH CCl CH Oacetyl 1-cyano- fluoroethyl cyclopropyl 169 penta- CF₃ Et Me CH CH CClCH O Me 1-cyano- fluoroethyl cyclopropyl 170 penta- methyl- Me H CH CHCCl CH O H 1-cyano- fluoroethyl sulphanyl cyclopropyl 171 penta- CF₃ EtEt CH CH CCl CH O H 1-cyano- fluoroethyl cyclopropyl 172 penta CF₃ Mecyano- CH CH CCl CH O H 1-cyano- fluoroethyl methyl cyclopropyl 173penta- methyl- Me H CH CH CCl CH O H 1-cyano- fluoroethyl sulphinylcyclopropyl 174 penta- CF₃ Pr Me CH CH CCl CH O Me 1-cyano- fluoroethylcyclopropyl 175 penta- CF₃ Pr Me CH CH CF CH O Me 1-cyano- fluoroethylcyclopropyl 176 penta- CF₃ Et Me CH CH CF CH O H 1-cyano- fluoroethylcyclopropyl 177 penta- methyl- Me H CH CH CCl CH O H 1-cyano fluoroethylsulphonyl cyclopropyl 178 penta- CF₃ Pr Et CH CH CCl CH O H 1-cyano-fluoroethyl cyclopropyl 179 penta- CF₃ Pr Et CH CH CCl CH O Et 1-cyano-fluoroethyl cyclopropyl 180 penta- CF₃ Et Et CH CH CCl CH O Et 1-cyano-fluoroethyl cyclopropyl 181 penta- CF₃ Me acetyl CH CH CCl CH O H1-cyano- fluoroethyl cyclopropyl 182 penta- CF₃ Me pyridin-3- CH CH CClCH O H 1-cyano- fluoroethyl ylmethyl cyclopropyl 183 penta- CF₃ Me2-methylprop- CH CH CCl CH O H 1-cyano- fluoroethyl 2-en-1-ylcyclopropyl 184 penta- CF₃ Me pyridin-4- CH CH CCl CH O H 1-cyano-fluoroethyl ylmethyl cyclopropyl 185 penta- CF₃ prop-2 H CH CH CCl CH OH 1-cyano- fluoroethyl yn-1-yl cyclopropyl 186 penta- CF₃ prop-2- H CHCH CCl CH O H 1-cyano- fluoroethyl en-1-yl cyclopropyl 187 penta- CF₃ MeH CH CF CBr CH O H 1-cyano- fluoroethyl cyclopropyl 188 penta- CF₃ Mepropionyl CH CH CCl CH O propionyl 1-cyano- fluoroethyl cyclopropyl 189penta- CF₃ Me H CH CH CCl CH O Et 1-cyano- fluoroethyl cyclopropyl 190penta- CF₃ Me H CH CH CCl CH O Me 1-cyano- fluoroethyl cyclopropyl 191penta- CF₃ Me isopropoxy- CH CH CCl CH O H 1-cyano- fluoroethyl carbonylcyclopropyl 192 penta- CF₃ 2,2,2-tri- H CH CH CCl CH O H 1-cyano-fluoroethyl fluoroethyl cyclopropyl 193 CF₃ CF₃ Me H CH CH CCl CH S H1-cyano- cyclopropyl 194 penta- CF₃ Me Me CH CH CCl CH S H 1-cyano-fluoroethyl cyclopropyl 195 penta- CF₃ Me H CH CH CCl CH S H 1-cyano-fluoroethyl cyclobutyl 196 penta- CF₃ Me Et CH CH CCl CH S H 1-cyano-fluoroethyl cyclopropyl 197 penta- CF₃ Me Me CH CH CCl CH S Me 1-cyanofluoroethyl cyclopropyl 198 penta- CF₃ Me Me CH CH CCl CH S Et 1-cyano-fluoroethyl cyclopropyl 199 1-chloro- Cl Me Me CH CH CCl CH S H 1-cyano-cyclopropyl cyclopropyl 200 CF₃ CF₃ Me Me CH CH CCl CH S H 1-cyanocyclopropyl 201 penta- CF₃ Me H CH CH CCl CH S H 1-cyano fluoroethylcyclopropyl 202 1-fluoro- Br Me H CH CH CCl CH S H 1-cyano cyclopropylcyclopropyl 203 CF₃ CF₃ Me H CH CBr CBr CH S H 1-cyano- cyclopropyl 204CF₃ CF₃ Me H CH CCl CBr CH S H 1-cyano- cyclopropyl 205 penta- CF₃ Me HCH CBr CCl CH S H 1-cyano- fluoroethyl cyclopropyl 206 penta- CF₃ Me HCH CH CBr CH S H 1-cyano- fluoroethyl cyclopropyl 207 penta- CF₃ Me H CHCH CCl CH S propionyl 1-cyano- fluoroethyl cyclopropyl 208 penta- CF₃ MeH CH CCl CBr CH S H 1-cyano- fluoroethyl cyclopropyl 209 1-fluoro- Cl MeH CH CH CCl CH S H 1-cyano- cyclopropyl cyclopropyl 210 penta- CF₃ Meacetyl CH CH CCl CH S acetyl 1-cyano- fluoroethyl cyclopropyl 211 penta-CF₃ Me methoxy- CH CH CCl CH S H 1-cyano- fluoroethyl carbonylcyclopropyl 212 penta- CF₃ Me ethoxy- CH CH CCl CH S H 1-cyano-fluoroethyl carbonyl cyclopropyl 213 penta- CF₃ Me methoxy- CH CH CCl CHS methoxy- 1-cyano- fluoroethyl carbonyl carbonyl cyclopropyl 214 penta-CF₃ Me ethoxy- CH CH CCl CH S ethoxy- 1-cyano fluoroethyl carbonylcarbonyl cyclopropyl 215 penta CF₃ Me 2,2-dimethyl- CH CH CCl CH S H1-cyano- fluoroethyl propanoyl cyclopropyl 216 penta- CF₃ Me H CH CMeCCl CH S H 1-cyano fluoroethyl cyclopropyl 217 penta- CF₃ Me H CH CH ClCH S H 1-cyano fluoroethyl cyclopropyl 218 penta- CF₃ Me prop-2- CH CHCCl CH S H 1-cyano- fluoroethyl yn-1-yl cyclopropyl 219 penta- CF₃ Me HCH CH CF CH S H 1-cyano- fluoroethyl cyclopropyl 220 penta- CF₃ Me4-chloro- CH CH CCl CH S H 1-cyano- fluoroethyl benzyl cyclopropyl 221penta- CF₃ Me isobutyryl CH CH CCl CH S H 1-cyano- fluoroethylcyclopropyl 222 penta- CF₃ Me but-2- CH CH CCl CH S H 1-cyano-fluoroethyl yn-1-yl cyclopropyl 223 penta- CF₃ Me benzyl CH CH CCl CH SH 1-cyano fluoroethyl cyclopropyl 224 penta- CF₃ Me pyridin-2- CH CH CClCH S H 1-cyano- fluoroethyl ylmethyl cyclopropyl 225 penta- CF₃ Mepropionyl CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 226 penta-CF₃ Et H CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 227 penta-CF₃ Pr H CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 228 penta-CF₃ Pr H CH CH CF CH S H 1-cyano- fluoroethyl cyclopropyl 229 penta- CF₃Et H CH CH CF CH S H 1-cyano- fluoroethyl cyclopropyl 230 penta- CF₃ EtMe CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 231 penta- CF₃ MeEt CH CBr CCl CH S H 1-cyano- fluoroethyl cyclopropyl 232 penta- CF₃ MeH CH CH CCl CH S acetyl 1-cyano- fluoroethyl cyclopropyl 233 penta- CF₃Et Me CH CH CCl CH S Me 1-cyano- fluoroethyl cyclopropyl 234 penta-methyl- Me H CH CH CCl CH S H 1-cyano- fluoroethyl sulphanyl cyclopropyl235 penta- CF₃ Et Et CH CH CCl CH S H 1-cyano- fluoroethyl cyclopropyl236 penta- CF₃ Me cyano- CH CH CCl CH S H 1-cyano- fluoroethyl methylcyclopropyl 237 penta- methyl- Me H CH CH CCl CH S H 1-cyano-fluoroethyl sulphinyl cyclopropyl 238 penta- CF₃ Pr Me CH CH CCl CH S Me1-cyano- fluoroethyl cyclopropyl 239 penta- CF₃ Pr Me CH CH CF CH S Me1-cyano- fluoroethyl cyclopropyl 240 penta- CF₃ Et Me CH CH CF CH S H1-cyano- fluoroethyl cyclopropyl 241 penta- methyl- Me H CH CH CCl CH SH 1-cyano- fluoroethyl sulphonyl cyclopropyl 242 penta- CF₃ Pr Et CH CHCCl CH S H 1-cyano- fluoroethyl cyclopropyl 243 penta- CF₃ Pr Et CH CHCCl CH S Et 1-cyano- fluoroethyl cyclopropyl 244 penta- CF₃ Et Et CH CHCCl CH S Et 1-cyano- fluoroethyl cyclopropyl 245 penta- CF₃ Me acetyl CHCH CCl CH S H 1-cyano- fluoroethyl cyclopropyl 246 penta- CF₃ Mepyridin-3- CH CH CCl CH S H 1-cyano- fluoroethyl ylmethyl cyclopropyl247 penta- CF₃ Me 2-methylprop- CH CH CCl CH S H 1-cyano- fluoroethyl2-en-1-yl cyclopropyl 248 penta- CF₃ Me pyridin-4- CH CH CCl CH S H1-cyano- fluoroethyl ylmethyl cyclopropyl 249 penta- CF₃ prop-2- H CH CHCCl CH S H 1-cyano- fluoroethyl yn-1-yl cyclopropyl 250 penta- CF₃prop-2- H CH CH CCl CH S H 1-cyano- fluoroethyl en-1-yl cyclopropyl 251penta- CF₃ Me H CH CF CBr CH S H 1-cyano- fluoroethyl cyclopropyl 252penta- CF₃ Me propionyl CH CH CCl CH S propionyl 1-cyano- fluoroethylcyclopropyl 253 penta- CF₃ Me H CH CH CCl CH S Et 1-cyano- fluoroethylcyclopropyl 254 penta- CF₃ Me H CH CH CCl CH S Me 1-cyano- fluoroethyl-cyclopropyl 255 penta- CF₃ Me isopropoxy- CH CH CCl CH S H 1-cyano-fluoroethyl carbonyl cyclopropyl 256 penta- CF₃ 2,2,2-tri- H CH CH CClCH S H 1-cyano- fluoroethyl fluoroethyl cyclopropyl

The stated mass is the peak of the isotope pattern of the [M+H]⁺ ion ofthe highest intensity; if the [M−H]⁻ ion was detected, the stated massis marked with ².

² The stated mass is the peak of the isotope pattern of the [M−H]⁻ ionof the highest intensity.

^(a)) Note regarding the determination of the log P values and massdetection: The determination of the given log P values was carried outin accordance with EEC Directive 79/831 Annex V.A8 by HPLC (HighPerformance Liquid Chromatography) on a reversed-phase column (C18).Agilent 1100 LC system; 50*4.6 Zorbax Eclipse Plus C18 1.8 micron;mobile phase A: acetonitrile (0.1% formic acid); mobile phase B: water(0.09% formic acid); linear gradient from 10% acetonitrile to 95%acetonitrile in 4.25 min, then 95% acetonitrile for a further 1.25 min;oven temperature 55° C.; flow rate: 2.0 ml/min. Mass detection is via anAgilend MSD system.

^(b)) Note regarding the determination of the log P values and massdetection: The stated log P values were determined in accordance withEEC Directive 79/831 Annex V.A8 by HPLC (High Performance LiquidChromatography) using a reversed-phase column (C18). HP1100; 50*4.6Zorbax Eclipse Plus C18 1.8 micron; mobile phase A: acetonitrile (0.1%formic acid); mobile phase B: water (0.08% formic acid); linear gradientfrom 5% acetonitrile to 95% acetonitrile in 1.70 min, then 95%acetonitrile for a further 1.00 min; oven temperature 55° C.; flow rate:2.0 ml/min Mass detection is via the mass detector Micromass ZQ2000 fromWaters.

NMR Data of Selected Examples

The ¹H-NMR data of selected examples are stated in the form of ¹H-NMRpeak lists. For each signal peak, the δ-value in ppm and the signalintensity in brackets are listed.

Ex. 3, solvent: [DMSO], spectrometer: 600.13 MHz 11.2357 (5.81); 9.4015(2.32); 7.9529 (0.33); 7.9112 (0.33); 7.6345 (0.34); 7.4603 (2.39);7.3952 (0.42); 7.3764 (0.35); 7.3658 (0.38); 7.3009 (0.7); 7.2887(0.72); 4.4308 (0.59); 4.4236 (0.6); 4.0461 (1.28); 4.0342 (3.7); 4.0223(3.71); 4.0105 (1.26); 3.853 (0.6); 3.8474 (0.42); 3.8307 (0.44); 3.7989(0.86); 3.788 (1.25); 3.7603 (10.68); 3.7331 (1.16); 3.726 (1.01);3.7196 (0.75); 3.7116 (0.53); 3.7053 (0.33); 3.459 (0.59); 3.4058(13.82); 3.3755 (1.92); 3.3496 (164.63); 3.3259 (1.89); 3.2237 (0.45);2.8908 (2.26); 2.7309 (1.92); 2.6212 (0.39); 2.6184 (0.58); 2.6154(0.72); 2.6125 (0.61); 2.5427 (1.49); 2.5244 (3.1); 2.5214 (3.56);2.5182 (3.84); 2.5093 (28.51); 2.5064 (58.78); 2.5034 (80.56); 2.5004(60.43); 2.4975 (29.82); 2.3903 (0.38); 2.3873 (0.5); 2.3843 (0.39);2.2647 (0.57); 2.2538 (0.97); 2.2442 (0.58); 2.2423 (0.63); 2.0871(0.62); 2.0233 (0.41); 2.0152 (0.44); 2.0134 (0.46); 1.9905 (16); 1.9096(1.12); 1.851 (0.52); 1.8378 (0.99); 1.7685 (0.38); 1.7588 (0.55);1.7475 (0.49); 1.7373 (0.4); 1.7288 (0.34); 1.7133 (0.34); 1.7077(0.35); 1.6908 (0.37); 1.6852 (0.36); 1.6645 (0.89); 1.6546 (1.09);1.6502 (1.34); 1.6452 (1.8); 1.6419 (1.74); 1.637 (1.45); 1.6253 (1.25);1.6174 (0.98); 1.6101 (0.88); 1.5994 (5.38); 1.5901 (11.8); 1.5856(12.84); 1.5767 (5.21); 1.55 (0.56); 1.4866 (0.63); 1.473 (0.68); 1.467(0.7); 1.4621 (0.62); 1.4595 (0.61); 1.4523 (0.5); 1.4479 (0.41); 1.4361(0.35); 1.3967 (1.99); 1.3471 (5.81); 1.2984 (1.34); 1.2782 (1.83);1.2518 (6.83); 1.2423 (12.83); 1.2384 (14.34); 1.2293 (8.19); 1.2043(2.47); 1.1864 (5.57); 1.1746 (9.7); 1.1627 (5.14); 1.1493 (0.89);1.1396 (0.87); 1.1361 (0.62); 1.1312 (0.65); 1.1158 (0.53); 1.111(0.55); 1.108 (0.57); 1.1022 (0.42); 1.0935 (0.51); 1.0875 (0.48);1.0847 (0.45); 1.0749 (0.38); 1.0668 (0.41); 1.0552 (0.36); 0.8965(0.36); 0.8891 (1.06); 0.8851 (0.68); 0.8808 (0.62); 0.8743 (0.76);0.8695 (0.73); 0.8627 (0.7); 0.8536 (0.94); 0.8421 (0.6); 0.8361 (0.4);0.8234 (0.34); −0.0001 (1.54) Ex. 4, solvent: [DMSO], spectrometer:399.95 MHz 19.9995 (0.35); 11.1852 (0.43); 7.6987 (0.97); 7.6759 (1.26);7.5988 (1.74); 7.5752 (1.65); 7.4867 (2.1); 7.3938 (0.43); 7.3652(0.84); 7.2019 (0.66); 5.7464 (4.97); 4.0662 (6.84); 4.0391 (1.88);4.0214 (2.04); 3.9933 (16); 3.595 (0.77); 3.5647 (0.67); 3.4575 (11.78);3.3059 (1902.13); 3.2823 (28.24); 3.251 (7.34); 3.1867 (1.32); 3.0111(0.86); 2.9377 (0.79); 2.9232 (0.87); 2.8698 (1.22); 2.7378 (0.55);2.6938 (0.68); 2.6741 (2.27); 2.6694 (2.78); 2.6647 (2.28); 2.5392(5.5); 2.5089 (156.27); 2.5047 (278.63); 2.5003 (354.49); 2.496(248.83); 2.3948 (0.32); 2.3317 (1.82); 2.327 (2.38); 2.0693 (1.78);2.0088 (0.37); 1.9867 (5.95); 1.9077 (1.11); 1.7114 (5.17); 1.6397(0.5); 1.5825 (0.5); 1.4849 (1.82); 1.3986 (7.92); 1.3522 (3.78); 1.2986(3.52); 1.259 (3.75); 1.2366 (4.08); 1.2171 (1.92); 1.1981 (2.64);1.1928 (3.24); 1.1751 (4.15); 1.1572 (2.51); 1.1005 (2.54); 0.8906(0.33); 0.8673 (0.4); 0.8547 (0.48); −0.0002 (5.05) Ex. 5, solvent:[DMSO], spectrometer: 601.6 MHz 7.7016 (0.47); 7.6872 (0.61); 7.646(0.57); 7.6419 (0.64); 7.6063 (0.37); 7.6024 (0.36); 7.5921 (0.54);7.5882 (0.56); 7.579 (0.6); 7.3776 (1.3); 7.3475 (0.34); 5.7617 (16);4.0701 (2.56); 4.0607 (0.79); 4.0345 (0.58); 4.0227 (0.63); 4.0108(0.48); 3.9904 (2.73); 3.4829 (0.66); 3.4608 (9.78); 3.4259 (0.46);3.3469 (320.39); 3.3232 (1.5); 3.2777 (0.75); 3.2493 (2.86); 3.2349(0.66); 3.1106 (0.9); 3.076 (0.68); 2.8649 (2.78); 2.6213 (0.57); 2.6183(0.8); 2.6153 (0.97); 2.6122 (0.82); 2.6093 (0.59); 2.543 (0.42); 2.5246(1.24); 2.5215 (1.51); 2.5184 (1.42); 2.5096 (29.65); 2.5066 (65.23);2.5035 (89.35); 2.5005 (63.63); 2.4975 (28.79); 2.3908 (0.39); 2.3877(0.55); 2.3847 (0.39); 2.0771 (1); 1.9902 (1.99); 1.6767 (1.95); 1.6734(2.2); 1.424 (0.34); 1.2981 (0.62); 1.2582 (0.83); 1.2356 (0.77); 1.1865(0.59); 1.1747 (1.16); 1.1629 (0.58); −0.0002 (5.52) Ex. 6, solvent:[DMSO], spectrometer: 399.95 MHz 9.5105 (1.11); 9.37 (2.71); 7.6861(0.89); 7.6648 (1.1); 7.6188 (1.04); 7.6126 (1.08); 7.5402 (2.64);7.5188 (3.08); 7.5037 (0.69); 7.4974 (0.6); 7.4823 (0.53); 7.4761(0.48); 7.4235 (2.42); 7.4171 (2.51); 7.2689 (1.57); 7.2623 (1.43);7.2476 (1.35); 7.2409 (1.22); 4.1197 (0.76); 4.1021 (1.01); 4.0852(1.27); 4.0686 (4.88); 4.0575 (1.57); 4.0496 (0.54); 4.0397 (3.72);4.0219 (3.71); 4.0041 (1.27); 3.8782 (10.99); 3.835 (0.33); 3.817(0.89); 3.7993 (1.08); 3.7824 (0.96); 3.7647 (0.74); 3.6837 (0.33);3.6654 (0.43); 3.6475 (0.38); 3.5854 (0.39); 3.5673 (0.46); 3.5489(0.34); 3.3007 (145.63); 3.2772 (2.79); 2.6695 (0.34); 2.5395 (0.82);2.5225 (1.85); 2.5092 (19.84); 2.5049 (35.06); 2.5004 (44.17); 2.4961(30.18); 2.4917 (14.34); 1.987 (16); 1.6127 (0.63); 1.6036 (1.61);1.5987 (1.68); 1.5905 (3.88); 1.5832 (3.24); 1.57 (1.36); 1.3041 (0.63);1.2906 (1.18); 1.2841 (1.18); 1.2696 (0.62); 1.2594 (0.5); 1.2375(1.04); 1.2307 (1.64); 1.2171 (3.03); 1.2106 (3.03); 1.1931 (4.97);1.1753 (9.03); 1.1575 (7.71); 1.1395 (7.05); 1.1216 (3.13); 0.962(1.16); 0.9444 (2.37); 0.9267 (1.1); −0.0002 (4.85) Ex. 7, solvent:[DMSO], spectrometer: 399.95 MHz 11.4754 (1.96); 9.5774 (3.66); 7.8103(3.62); 7.804 (4.04); 7.7228 (1.61); 7.7165 (1.38); 7.701 (2.26); 7.6946(2.08); 7.606 (3.39); 7.5841 (2.38); 4.0559 (1.18); 4.0345 (16); 4.0204(3.51); 4.0025 (1.13); 3.3203 (18.4); 2.7184 (0.84); 2.7027 (1.21);2.6977 (1.45); 2.6851 (1.56); 2.6827 (1.57); 2.6699 (2.11); 2.6503(1.2); 2.5102 (14.26); 2.5059 (28.52); 2.5014 (37.33); 2.4969 (26.79);2.4927 (12.96); 2.4835 (1.57); 2.4608 (2.15); 2.4525 (1.25); 2.4404(1.55); 2.4316 (1.69); 2.4084 (0.97); 2.1036 (0.56); 2.0953 (0.6); 2.085(1.52); 2.0732 (1.03); 2.0651 (2.45); 2.058 (1.57); 2.0451 (1.65);2.0352 (0.77); 2.0288 (0.39); 2.0252 (0.41); 2.0196 (0.4); 1.9889(13.81); 1.1925 (3.78); 1.1747 (7.53); 1.1569 (3.66); −0.0002 (0.53) Ex.8, solvent: [CD3CN], spectrometer: 399.95 MHz 7.6396 (0.36); 7.5867(0.51); 7.5653 (0.89); 7.544 (0.65); 7.5381 (0.86); 7.5157 (0.67);7.5093 (0.52); 7.4941 (0.53); 7.4875 (0.63); 7.4768 (0.79); 7.3968(2.11); 7.3753 (2.53); 7.3065 (1.94); 7.2998 (2.09); 7.1716 (1.4);7.1649 (1.32); 7.1502 (1.17); 7.1434 (1.07); 3.9903 (3.54); 3.8495(10.24); 3.4568 (16); 3.2228 (4.6); 2.1412 (168.83); 2.1318 (2.24);2.1187 (0.37); 2.1125 (0.33); 2.1063 (0.38); 1.9749 (1.26); 1.9632(92.07); 1.9513 (18.04); 1.9451 (33.99); 1.9389 (49.06); 1.9328 (33.45);1.9266 (16.89); 1.7909 (0.5); 1.5939 (0.45); 1.5781 (1.51); 1.5737(1.53); 1.5637 (2.7); 1.5577 (3.02); 1.5476 (0.89); 1.5443 (0.86);1.3605 (0.47); 1.3468 (0.97); 1.3398 (1.12); 1.3254 (0.39); 1.2938(1.35); 1.2881 (1.36); 1.2837 (1.68); 1.2798 (2.1); 1.2733 (1.74);1.2636 (1.03); −0.0002 (5.39) Ex. 9, solvent: [CD3CN], spectrometer:601.6 MHz 9.3097 (0.56); 7.77 (3.79); 7.7657 (4.14); 7.6801 (2.48);7.6757 (2.25); 7.6656 (2.92); 7.6612 (2.72); 7.6146 (1.14); 7.4969(4.24); 7.4825 (3.68); 3.981 (16); 2.1615 (181.62); 2.0874 (0.35);2.0771 (1.5); 2.0604 (0.46); 2.0563 (0.85); 2.0522 (1.16); 2.048 (0.87);2.044 (0.44); 1.9735 (2.01); 1.9659 (259.46); 1.9576 (3.22); 1.9536(3.65); 1.9499 (74.77); 1.9457 (141.93); 1.9416 (218.7); 1.9375(150.41); 1.9334 (73.06); 1.9287 (2.12); 1.9246 (0.98); 1.8507 (1.44);1.8351 (0.43); 1.831 (0.84); 1.8269 (1.17); 1.8227 (0.83); 1.8186(0.43); 1.5805 (1.94); 1.5707 (4.1); 1.5665 (4.32); 1.5572 (2.31); 1.351(2.23); 1.3416 (4); 1.3375 (4.07); 1.3276 (1.81); 0.9112 (1.45); 0.0053(0.53); −0.0002 (20.71); −0.0057 (0.61) Ex. 10, solvent: [DMSO],spectrometer: 600.13 MHz 11.4592 (3.78); 9.4859 (4.45); 7.7721 (3.8);7.7678 (4.24); 7.7112 (2.06); 7.7068 (1.78); 7.6966 (2.55); 7.6922(2.36); 7.5881 (4.49); 7.5736 (3.69); 4.0356 (0.65); 4.0285 (16); 3.3215(12.57); 2.5227 (0.37); 2.5196 (0.46); 2.5165 (0.45); 2.5077 (11.12);2.5047 (24.25); 2.5017 (33.57); 2.4986 (24.06); 2.4956 (10.94); 1.989(1.5); 1.6018 (1.64); 1.5924 (3.8); 1.5879 (4.14); 1.5789 (1.69); 1.2696(1.81); 1.2604 (3.74); 1.256 (4.13); 1.2464 (1.5); 1.1871 (0.41); 1.1753(0.83); 1.1634 (0.41); 0.0053 (0.46); −0.0001 (14.7); −0.0057 (0.44) Ex.11, solvent: [CD3CN], spectrometer: 601.6 MHz 9.4276 (0.94); 8.1604(0.81); 8.1562 (0.84); 8.0909 (3.21); 8.0868 (3.24); 7.8499 (0.65);7.8457 (0.65); 7.6042 (1.17); 7.5896 (3.34); 7.5855 (3.31); 3.99 (0.48);3.9775 (16); 2.2102 (11.21); 2.0881 (0.39); 2.0779 (0.4); 2.0656 (0.66);2.0611 (0.41); 2.057 (0.54); 2.0529 (0.65); 2.0486 (0.62); 2.048 (0.62);2.0447 (0.36); 1.9732 (0.39); 1.9666 (16.06); 1.9584 (0.96); 1.9542(1.36); 1.9506 (29.13); 1.9464 (53.99); 1.9423 (82.18); 1.9382 (57.22);1.9341 (28.42); 1.9294 (1.09); 1.9253 (0.59); 1.8317 (0.39); 1.8276(0.51); 1.8234 (0.37); 1.5826 (1.54); 1.5728 (3.25); 1.5686 (3.38);1.5593 (1.89); 1.3599 (1.74); 1.3506 (3.08); 1.3464 (3.24); 1.3366(1.49); 0.911 (0.48); −0.0002 (0.46) Ex. 12, solvent: [CD3CN],spectrometer: 601.6 MHz 9.4577 (0.94); 7.9506 (3.67); 7.9465 (3.74);7.6252 (1.29); 7.6178 (0.41); 7.5485 (3.85); 7.5444 (3.76); 5.4498(1.24); 4.1225 (0.39); 3.9907 (0.48); 3.9784 (16); 2.2016 (26.81);2.0656 (0.9); 2.0571 (0.36); 2.053 (0.47); 2.0479 (0.79); 1.9732 (1.48);1.9668 (2.89); 1.9586 (0.78); 1.9572 (0.41); 1.9544 (1.17); 1.9507(24.16); 1.9466 (45.51); 1.9424 (67.8); 1.9383 (46.53); 1.9342 (23.27);1.9296 (0.68); 1.8277 (0.39); 1.5858 (1.78); 1.576 (3.73); 1.5718 (3.9);1.5625 (2.15); 1.3635 (2.04); 1.3541 (3.59); 1.3499 (3.77); 1.3401(1.77); 1.269 (0.34); 1.2159 (0.42); 1.2041 (0.83); 1.1922 (0.4); 0.911(0.44) Ex. 13, solvent: [CD3CN], spectrometer: 399.95 MHz 9.425 (1.09);8.1057 (3.59); 8.0995 (3.63); 8.089 (0.38); 8.0828 (0.33); 7.9667(0.34); 7.6477 (3.95); 7.6415 (4.02); 7.626 (1.54); 7.6058 (0.49);7.5997 (0.42); 7.5882 (0.4); 7.582 (0.48); 7.4416 (0.5); 4.1118 (0.33);4.0862 (1.68); 4.0683 (4.78); 4.0505 (4.77); 4.0327 (1.64); 3.9761 (16);3.8931 (3.57); 2.1489 (347.53); 2.1318 (7.91); 2.1127 (2.21); 2.1065(2.07); 2.1003 (1.56); 2.0941 (1.09); 2.0486 (0.56); 2.0434 (0.54);1.9712 (32.63); 1.9634 (416.05); 1.9514 (67.15); 1.9453 (119.86); 1.9391(167.42); 1.9329 (114.6); 1.9267 (58.47); 1.7911 (2.41); 1.7799 (0.49);1.7737 (0.78); 1.7675 (1.01); 1.7614 (0.72); 1.7553 (0.42); 1.6282(0.54); 1.6129 (1.02); 1.6069 (1.1); 1.604 (0.72); 1.5923 (0.84); 1.5869(1.9); 1.5726 (4.35); 1.5656 (4.47); 1.5518 (2.49); 1.5116 (0.39);1.3551 (2.45); 1.3413 (4.31); 1.3343 (4.21); 1.3295 (1.9); 1.3202 (2.1);1.3078 (0.68); 1.2852 (0.55); 1.2708 (1.26); 1.2216 (6.04); 1.2038(11.75); 1.1859 (5.85); 0.9117 (0.79); 0.008 (0.82); −0.0002 (18.6);−0.0085 (0.72) Ex. 14, solvent: [DMSO], spectrometer: 601.6 MHz 11.475(2.8); 9.482 (4.01); 7.7377 (4.18); 7.7332 (5.35); 7.7173 (3.05); 7.6669(0.49); 7.6647 (0.45); 7.6299 (2.01); 7.6257 (1.86); 7.6155 (1.61);7.6111 (1.54); 4.046 (0.85); 4.0342 (3.8); 4.0263 (16); 4.0225 (3.74);4.0105 (0.89); 3.3858 (0.71); 3.3809 (1.58); 3.3784 (1.63); 3.3578(1678.47); 3.3341 (3.39); 3.0116 (0.41); 2.8065 (0.44); 2.6184 (0.64);2.6153 (0.91); 2.6123 (0.64); 2.543 (0.47); 2.5247 (1.22); 2.5216 (1.5);2.5185 (1.46); 2.5097 (46.46); 2.5066 (102.74); 2.5036 (142.42); 2.5006(100.14); 2.4975 (44.69); 2.3908 (0.62); 2.3877 (0.87); 2.3847 (0.62);2.0764 (1.87); 1.99 (10.94); 1.6062 (1.8); 1.5968 (4.05); 1.5923 (4.48);1.5834 (1.81); 1.3972 (8.53); 1.272 (1.92); 1.2628 (3.88); 1.2584(4.36); 1.2489 (1.8); 1.1863 (2.99); 1.1745 (5.92); 1.1626 (2.92);0.0053 (0.68); −0.0002 (22.51); −0.0058 (0.62) Ex. 15, solvent: [CD3CN],spectrometer: 601.6 MHz 7.6736 (3.25); 7.6594 (3.63); 7.6529 (0.62);7.6383 (0.67); 7.5026 (1.73); 7.476 (1.42); 7.4719 (1.04); 7.4618(1.32); 7.4578 (1.01); 7.4501 (0.41); 7.4349 (0.37); 5.3097 (0.35);5.2976 (0.39); 4.0762 (0.87); 4.0644 (2.65); 4.0525 (2.74); 4.0407(0.93); 3.9757 (0.91); 3.9408 (5.26); 3.9313 (16); 2.8568 (0.62); 2.8452(1.86); 2.8333 (1.86); 2.8212 (0.7); 2.5123 (0.35); 2.4998 (1.1); 2.4874(1.07); 2.4749 (0.42); 2.2936 (1.21); 2.2824 (1.31); 2.2699 (0.62);2.2265 (0.62); 2.2149 (0.61); 2.1802 (0.36); 2.1739 (0.55); 2.1673(0.84); 2.1535 (644.37); 2.1294 (0.59); 2.1215 (0.48); 2.0601 (0.87);2.0561 (1.51); 2.0519 (2.22); 2.0478 (1.52); 2.0437 (0.77); 1.9727(12.69); 1.9656 (21.18); 1.9575 (11.83); 1.9534 (14.58); 1.9496 (147.5);1.9454 (266.85); 1.9413 (402.32); 1.9372 (276.01); 1.9331 (137.69);1.9244 (1.96); 1.8503 (0.47); 1.8347 (1.84); 1.8307 (2.73); 1.8266(3.2); 1.8225 (2.22); 1.8184 (1.32); 1.7246 (0.62); 1.7188 (0.99);1.7132 (0.82); 1.6902 (1.73); 1.6658 (1); 1.6361 (0.55); 1.6214 (0.44);1.6159 (0.49); 1.5864 (0.66); 1.5822 (0.66); 1.5728 (0.47); 1.5666(0.46); 1.5571 (0.39); 1.5334 (1.65); 1.5063 (1.02); 1.5029 (0.92);1.4777 (0.65); 1.4659 (0.65); 1.3852 (0.49); 1.3515 (0.42); 1.3403(1.5); 1.3284 (0.54); 1.2851 (2.14); 1.2701 (1.88); 1.2384 (0.36);1.2227 (0.53); 1.2158 (4.13); 1.2039 (7.13); 1.1963 (1.02); 1.1921(4.09); 1.1765 (0.52); 1.1568 (0.64); 1.1488 (1.95); 1.1363 (4.5);1.1315 (0.55); 1.1238 (2.55); 1.1152 (0.75); 1.1112 (1.54); 1.1021(0.47); 1.0987 (0.78); 1.0915 (6.22); 1.0797 (12.97); 1.0677 (6.14);1.0509 (0.37); 1.0462 (0.5); 1.0418 (0.48); 1.0022 (0.57); 0.9849(0.79); 0.9637 (0.69); 0.949 (4.67); 0.9431 (1.35); 0.9371 (10.26);0.9313 (2.24); 0.9244 (5.69); 0.9194 (1.11); 0.9121 (1.74); 0.8817(0.48); 0.0964 (0.45); 0.0053 (3.79); −0.0002 (131.79); −0.0058 (3.52);−0.1 (0.49) Ex. 16, solvent: [DMSO], spectrometer: 601.6 MHz 11.6171(2.98); 9.5642 (4.11); 8.0041 (4.64); 8.0001 (4.81); 7.5795 (3.62);7.5754 (3.58); 4.377 (0.35); 4.3686 (0.7); 4.3601 (0.34); 4.0417 (16);4.0342 (2.77); 4.0223 (2.5); 4.0105 (0.81); 3.9261 (1.01); 3.4494(0.63); 3.4409 (0.64); 3.4378 (0.67); 3.4293 (0.66); 3.3467 (410.03);3.3231 (3.18); 2.6178 (0.42); 2.6148 (0.6); 2.6118 (0.44); 2.5425(0.44); 2.524 (1.29); 2.521 (1.64); 2.5178 (1.9); 2.509 (30.94); 2.5061(65.8); 2.5031 (89.43); 2.5 (63.28); 2.497 (28.23); 2.3902 (0.4); 2.3872(0.55); 2.3842 (0.39); 2.0769 (0.6); 1.99 (10.77); 1.9093 (0.47); 1.6161(1.9); 1.6067 (4.15); 1.6022 (4.51); 1.5933 (1.81); 1.3972 (13.57);1.3139 (0.32); 1.2846 (2.01); 1.2754 (3.98); 1.271 (4.39); 1.2614(1.64); 1.1863 (2.93); 1.1745 (6.06); 1.1627 (2.93); 1.0665 (1.46);1.0549 (2.75); 1.0433 (1.33); 0.0052 (0.71); −0.0002 (20.09); −0.0057(0.51) Ex. 17, solvent: [DMSO], spectrometer: 399.95 MHz 10.9164 (2.69);9.4701 (3.13); 7.8379 (2.16); 7.8316 (2.46); 7.7664 (1.22); 7.76 (1.05);7.7445 (1.48); 7.7381 (1.32); 7.5569 (3.32); 7.5351 (2.79); 5.7527 (16);4.0382 (0.59); 4.0204 (0.58); 3.9311 (10.48); 3.9291 (10.23); 3.4476(0.32); 3.4238 (0.79); 3.3995 (1.41); 3.3529 (444.16); 3.2649 (0.45);2.6723 (0.35); 2.5255 (1.04); 2.5123 (20.85); 2.5078 (42.03); 2.5032(55.95); 2.4986 (40.59); 2.4941 (19.88); 2.3299 (0.35); 2.0728 (0.88);1.9887 (2.51); 1.6084 (1.2); 1.5942 (2.85); 1.5874 (2.99); 1.5741(1.42); 1.4745 (0.54); 1.4586 (1.66); 1.4548 (1.64); 1.4399 (0.7);1.4294 (0.58); 1.4133 (1.6); 1.4094 (1.68); 1.3975 (0.83); 1.3948(0.79); 1.2663 (1.44); 1.2525 (2.82); 1.246 (3.04); 1.2314 (1.24);1.1927 (0.77); 1.1749 (1.45); 1.1571 (0.71); 1.129 (0.6); 1.1124 (1.86);1.1085 (2.26); 1.0923 (2.2); 1.0884 (1.8); 1.0706 (0.5) Ex. 18, solvent:[DMSO], spectrometer: 601.6 MHz 7.8045 (2.23); 7.7904 (2.42); 7.6562(0.38); 4.0456 (0.8); 4.0338 (2.39); 4.0304 (0.69); 4.0219 (3.08); 4.015(16); 3.3608 (569.24); 3.3375 (3.07); 2.6187 (0.62); 2.6157 (0.85);2.6127 (0.62); 2.5434 (0.54); 2.525 (1.66); 2.5219 (2.15); 2.5188 (2.4);2.51 (45.96); 2.507 (97.64); 2.504 (134.23); 2.5009 (97.3); 2.4979(44.27); 2.4056 (15.53); 2.3974 (1.27); 2.3945 (0.66); 2.3911 (0.88);2.3882 (1.2); 2.3851 (0.77); 2.3823 (0.42); 2.2183 (1.21); 2.0872(0.45); 2.0779 (2.65); 2.0487 (3.59); 2.0305 (0.77); 2.0256 (0.48);1.9905 (10.01); 1.9538 (0.39); 1.9098 (4.41); 1.8867 (0.87); 1.8814(0.87); 1.3969 (14.61); 1.2345 (0.46); 1.1862 (2.73); 1.1744 (5.37);1.1653 (0.38); 1.1625 (2.65); −0.0002 (9.42) Ex. 19, solvent: [DMSO],spectrometer: 399.95 MHz 9.6008 (2.87); 7.7336 (2.68); 7.7122 (3.27);7.6828 (2.15); 7.6766 (2.25); 7.518 (1.37); 7.5117 (1.26); 7.4968(1.12); 7.4904 (1.05); 4.066 (10.48); 4.0381 (0.83); 4.0203 (1.07);4.0026 (0.33); 3.6767 (16); 3.487 (0.45); 3.4643 (0.44); 3.4467 (0.79);3.4391 (0.81); 3.4231 (1.05); 3.4136 (1.13); 3.3468 (882.82); 3.3224(20.56); 3.2828 (0.63); 2.6764 (0.54); 2.6718 (0.74); 2.6674 (0.52);2.542 (0.61); 2.5249 (2.21); 2.5118 (42.56); 2.5073 (85.34); 2.5028(113.7); 2.4982 (82.44); 2.4937 (40); 2.3341 (0.49); 2.3295 (0.72);2.3249 (0.52); 2.0729 (3.68); 1.9886 (3.32); 1.6558 (0.33); 1.6144(1.37); 1.6001 (2.7); 1.5932 (2.9); 1.5801 (1.41); 1.2938 (1.3); 1.2802(2.57); 1.2735 (2.8); 1.2588 (1.33); 1.2356 (0.78); 1.1925 (0.98);1.1748 (2); 1.1569 (1); 0.008 (1.05); −0.0002 (28.19); −0.0085 (1.08)Ex. 20, solvent: [DMSO], spectrometer: 601.6 MHz 9.6087 (4.57); 7.7293(4.27); 7.7152 (4.9); 7.6801 (2.65); 7.676 (2.67); 7.4972 (1.63); 7.493(1.51); 7.4831 (1.43); 7.4788 (1.38); 4.3682 (0.58); 4.1597 (0.43);4.1483 (1); 4.1369 (1.24); 4.1257 (1.28); 4.1143 (1); 4.1025 (0.47);4.0779 (16); 4.0458 (0.46); 4.0339 (1.37); 4.0221 (1.98); 4.0103 (0.59);3.449 (0.49); 3.4406 (0.49); 3.4374 (0.48); 3.429 (0.51); 3.3716 (1.66);3.3457 (1847.32); 3.3222 (24.12); 2.6205 (0.63); 2.6176 (1.47); 2.6145(2.05); 2.6115 (1.48); 2.6085 (0.63); 2.5422 (0.95); 2.5239 (2.46);2.5208 (3.15); 2.5177 (3.1); 2.5088 (106.25); 2.5058 (238.45); 2.5028(334.46); 2.4997 (242.59); 2.4967 (110.57); 2.393 (0.68); 2.39 (1.49);2.3869 (2.09); 2.3839 (1.49); 2.3808 (0.69); 2.0766 (4.02); 1.9898(5.37); 1.6109 (1.83); 1.6016 (3.88); 1.5971 (4.4); 1.5882 (2.19);1.5763 (0.45); 1.2977 (0.37); 1.2859 (1.83); 1.2767 (3.71); 1.2723(4.13); 1.2627 (1.75); 1.2579 (0.87); 1.2535 (1.01); 1.2499 (0.7);1.2416 (1.16); 1.2342 (1.17); 1.23 (0.84); 1.1861 (1.54); 1.1742 (3.2);1.1624 (1.62); 1.1496 (0.36); 1.0663 (1.12); 1.0546 (2); 1.043 (1.01);0.9965 (6.51); 0.9847 (13.73); 0.973 (6.33); 0.0965 (0.41); 0.0053(3.4); −0.0002 (125.56); −0.0058 (3.65); −0.1001 (0.45) Ex. 21, solvent:[DMSO], spectrometer: 399.95 MHz 7.7082 (2.45); 7.6866 (3.64); 7.6836(2.1); 7.6766 (1.8); 7.663 (0.46); 7.5662 (0.33); 7.5492 (1.41); 7.5429(1.29); 7.5279 (1.11); 7.5216 (1.06); 4.0591 (10.46); 4.038 (1.4);4.0203 (2.19); 4.0025 (0.48); 3.7168 (0.33); 3.679 (15.83); 3.6733(4.07); 3.6676 (16); 3.4322 (0.35); 3.3435 (321.55); 3.3363 (458.6);3.2717 (0.52); 3.1751 (0.88); 3.162 (0.79); 2.6807 (0.32); 2.676 (0.65);2.6714 (0.93); 2.6667 (0.65); 2.5415 (0.74); 2.5246 (2.58); 2.5114(50.63); 2.5069 (102.7); 2.5023 (137.44); 2.4977 (99.21); 2.4931(48.14); 2.3337 (0.63); 2.3291 (0.88); 2.3244 (0.63); 2.0731 (1.7);1.9885 (5.54); 1.9008 (1.74); 1.8954 (2.04); 1.6574 (0.47); 1.6142(1.05); 1.5995 (1.75); 1.5933 (1.89); 1.2728 (0.35); 1.2585 (0.57);1.2522 (0.48); 1.2358 (0.96); 1.1925 (1.64); 1.1747 (3.39); 1.1569(1.68); −0.0002 (6.5) Ex. 22, solvent: [DMSO], spectrometer: 601.6 MHz7.7596 (0.35); 7.711 (3.38); 7.6968 (4.08); 7.6797 (1.48); 7.5444 (1.6);7.5402 (1.49); 7.5303 (1.29); 7.526 (1.24); 4.3683 (0.44); 4.2593(0.33); 4.2476 (0.33); 4.1566 (0.43); 4.1449 (0.94); 4.1332 (1.15);4.1243 (1.15); 4.1129 (1.05); 4.1045 (0.75); 4.0946 (1.48); 4.0828(3.99); 4.0686 (16); 4.0595 (1.27); 4.034 (0.45); 4.0221 (0.58); 4.0158(0.43); 4.0103 (0.4); 3.449 (0.38); 3.4406 (0.38); 3.4374 (0.4); 3.429(0.41); 3.3742 (1.02); 3.3457 (1563.22); 3.322 (28.53); 2.6206 (0.69);2.6176 (1.46); 2.6146 (2.04); 2.6115 (1.44); 2.6085 (0.64); 2.5423(1.22); 2.5239 (3.79); 2.5208 (5.05); 2.5176 (5.93); 2.5089 (109.54);2.5059 (236.08); 2.5028 (323.23); 2.4997 (233.05); 2.4967 (103.3);2.4766 (0.35); 2.3931 (0.66); 2.39 (1.43); 2.387 (2); 2.3839 (1.38);2.3809 (0.63); 2.0767 (3.48); 1.9899 (1.42); 1.9031 (2.58); 1.6908(0.35); 1.6696 (0.36); 1.6437 (0.33); 1.6184 (0.43); 1.5761 (1.67);1.2579 (0.49); 1.2485 (0.35); 1.2344 (1.07); 1.2265 (0.65); 1.2146(1.08); 1.2029 (0.52); 1.1861 (0.52); 1.1743 (1.03); 1.1705 (0.37);1.1625 (0.52); 1.1492 (0.42); 1.0663 (0.87); 1.0547 (1.54); 1.043(0.81); 1.0013 (6.44); 0.9895 (13.63); 0.9848 (1.07); 0.9817 (2.21);0.9778 (6.34); 0.97 (0.97); 0.9557 (6.62); 0.9439 (14.2); 0.9321 (6.4);0.0052 (3.03); −0.0002 (83.54); −0.0058 (2.47) Ex. 23, solvent: [DMSO],spectrometer: 399.95 MHz 9.5605 (1.88); 7.757 (1.46); 7.7355 (1.78);7.6605 (0.8); 7.545 (0.66); 7.5386 (0.61); 7.5238 (0.55); 7.5174 (0.52);4.058 (1.05); 4.0402 (3.29); 4.0271 (6.99); 4.0225 (4.44); 4.0046(1.09); 3.3924 (24.23); 3.386 (32.63); 3.3799 (54.59); 3.377 (71.91);2.5111 (7.26); 2.5069 (9.99); 2.5034 (6.54); 1.9898 (14.31); 1.6154(0.75); 1.6011 (1.63); 1.5941 (1.77); 1.5811 (0.79); 1.3053 (0.83);1.2917 (1.6); 1.2849 (1.74); 1.2704 (0.67); 1.2049 (0.71); 1.1943 (4);1.1765 (8.08); 1.1587 (3.94); 1.1133 (2.92); 1.012 (16); −0.0002 (1.63)Ex. 24, solvent: [DMSO], spectrometer: 399.95 MHz 19.0481 (0.34); 12.999(0.34); 11.6718 (0.32); 11.3817 (2.98); 11.2103 (0.33); 10.7432 (0.44);10.1704 (0.38); 9.4484 (4.12); 9.4182 (0.34); 7.674 (2.45); 7.6678(2.75); 7.5767 (3.19); 7.5699 (2.9); 7.471 (0.33); 4.1638 (0.77); 4.0557(0.89); 4.0379 (3.26); 4.0189 (16); 4.0023 (1.06); 3.9243 (2.59); 3.4462(0.32); 3.409 (0.48); 3.3939 (0.61); 3.3326 (387.86); 3.3263 (665.26);3.3027 (8.07); 2.675 (1.43); 2.6707 (2.09); 2.6661 (1.44); 2.5406(0.85); 2.5238 (3.39); 2.5058 (218.8); 2.5017 (290.84); 2.4581 (0.39);2.4169 (0.78); 2.3781 (14.51); 2.3549 (0.74); 2.3328 (1.45); 2.3283(2.04); 2.3241 (1.4); 2.3115 (0.8); 2.2563 (0.65); 2.0733 (1.71); 1.9884(10.86); 1.6699 (0.36); 1.6549 (0.65); 1.6463 (0.63); 1.6341 (0.43);1.6004 (1.6); 1.5859 (3.6); 1.5791 (3.91); 1.5661 (1.86); 1.3966 (0.4);1.3312 (0.52); 1.318 (0.62); 1.3117 (0.71); 1.2978 (0.44); 1.2651(1.73); 1.2518 (3.47); 1.2451 (3.89); 1.2311 (1.8); 1.217 (0.45); 1.1924(3.07); 1.1745 (5.77); 1.1568 (2.92); 0.0081 (1.01); −0.0002 (34.96);−0.0085 (1.17); −3.0246 (0.33) Ex. 25, solvent: [CD3CN], spectrometer:601.6 MHz 7.9022 (3.82); 7.8879 (4.08); 7.6652 (3.91); 7.6609 (4.01);7.52 (1.53); 7.4355 (2.47); 7.4312 (2.34); 7.4212 (2.34); 7.4169 (2.23);4.0758 (0.58); 4.064 (1.8); 4.0521 (1.78); 4.0403 (0.62); 3.9724 (16);3.893 (0.72); 2.1596 (251.61); 2.0611 (0.72); 2.057 (1.25); 2.0529(1.77); 2.0487 (1.27); 2.0447 (0.68); 1.9732 (8.88); 1.9666 (29.58);1.9584 (12.1); 1.9543 (16.7); 1.9505 (119.09); 1.9464 (214.31); 1.9423(320.41); 1.9382 (222.08); 1.9341 (110.06); 1.9254 (2.33); 1.917 (0.76);1.9128 (0.53); 1.9086 (0.36); 1.8357 (0.67); 1.8317 (1.23); 1.8275(1.73); 1.8234 (1.22); 1.8193 (0.63); 1.5855 (1.79); 1.5758 (4.1);1.5715 (4.17); 1.5623 (2.12); 1.382 (2.17); 1.3727 (4.02); 1.3684(4.12); 1.3586 (1.71); 1.2691 (1.08); 1.2158 (2.25); 1.204 (4.73);1.1922 (2.22); 0.0053 (1.55); −0.0002 (41.75); −0.0058 (1.45) Ex. 26,solvent: [DMSO], spectrometer: 399.95 MHz 14.5618 (0.37); 14.1854(0.35); 9.5578 (1.5); 9.4271 (4.93); 9.2998 (0.36); 9.182 (0.38); 7.7634(0.46); 7.7069 (1.14); 7.6847 (2.16); 7.5756 (3.33); 7.5541 (4.12);7.5266 (0.76); 7.4862 (3.47); 7.3446 (0.38); 7.3053 (0.47); 7.275 (2.4);7.2683 (2.29); 7.2533 (2.08); 7.2469 (1.92); 6.2641 (0.37); 4.9734(1.6); 4.9321 (1.8); 4.5811 (1.98); 4.537 (3.53); 4.1428 (0.59); 4.0566(5.17); 4.0378 (2.79); 4.0204 (2.99); 4.0026 (0.88); 3.9185 (0.48);3.8903 (16); 3.8573 (0.39); 3.427 (1.33); 3.3939 (4.28); 3.3402(400.48); 3.3359 (525.28); 3.3323 (787.02); 3.3084 (5.46); 3.272 (0.61);3.2561 (0.46); 3.247 (0.37); 3.1263 (0.42); 2.7317 (0.36); 2.6709(1.52); 2.5869 (0.39); 2.5415 (0.81); 2.5019 (262.13); 2.3291 (1.73);2.0734 (1.24); 1.9884 (10.84); 1.5957 (5.63); 1.5917 (5.18); 1.576(1.96); 1.5443 (0.37); 1.3969 (0.85); 1.278 (1.69); 1.2718 (1.78);1.2585 (0.99); 1.2348 (1.26); 1.2215 (2.19); 1.207 (4.49); 1.2015(4.56); 1.1924 (3.48); 1.1863 (1.89); 1.1747 (5.89); 1.1566 (2.78);1.1479 (0.43); 0.8742 (0.46); 0.8572 (0.47); −0.0002 (33.26); −3.0698(0.43) Ex. 27, solvent: [DMSO], spectrometer: 399.95 MHz 11.4041 (3.19);9.3381 (2.87); 7.9571 (1.61); 7.9504 (1.81); 7.9418 (1.7); 7.9349(1.72); 7.8013 (0.9); 7.7942 (0.92); 7.7904 (1.04); 7.7832 (0.95);7.7788 (1.01); 7.7717 (1.07); 7.7681 (1.06); 7.7609 (0.81); 7.4187(1.73); 7.3949 (2.44); 7.3715 (1.58); 4.0894 (4.37); 4.0563 (1.29);4.0384 (4.43); 4.0308 (15.34); 4.0206 (4.05); 4.0029 (1.29); 3.5817(0.36); 3.5615 (0.4); 3.5454 (0.49); 3.3749 (56.68); 3.1998 (0.54);3.1712 (0.38); 3.0611 (0.42); 2.6762 (0.39); 2.6716 (0.49); 2.6674(0.4); 2.5249 (0.94); 2.5068 (58.75); 2.5027 (78.81); 2.4986 (54.63);2.3339 (0.38); 2.3294 (0.51); 2.325 (0.35); 1.9888 (16); 1.9093 (0.63);1.5971 (1.56); 1.5828 (3.77); 1.5759 (3.95); 1.5626 (1.86); 1.2977(2.14); 1.2839 (3.86); 1.2772 (4.13); 1.2626 (1.77); 1.2355 (1.38);1.1928 (4.29); 1.175 (8.54); 1.1572 (4.24); −0.0002 (11.21); −0.0085(0.33) Ex. 28, solvent: [DMSO], spectrometer: 399.95 MHz 9.475 (0.97);9.3642 (5.1); 9.3069 (0.43); 8.7987 (0.37); 7.6689 (0.73); 7.5838(0.66); 7.5622 (0.78); 7.4575 (2.92); 7.4414 (4.62); 7.4312 (1.02);7.4246 (5.68); 7.42 (6.85); 7.4037 (7.53); 7.3379 (0.95); 7.3163 (1.1);7.2661 (6.47); 7.2452 (5.07); 7.0778 (1.07); 7.0631 (0.5); 7.0582(0.85); 6.9726 (1.86); 6.966 (1.92); 6.9512 (1.68); 6.945 (1.6); 5.4201(2.11); 5.3833 (2.31); 4.9665 (0.6); 4.9267 (2.61); 4.8893 (2.28);4.0551 (0.77); 4.045 (2.59); 4.0382 (2.1); 4.02 (1.77); 4.0026 (0.63);3.8971 (16); 3.4603 (0.41); 3.4347 (0.7); 3.4009 (1.13); 3.3491(582.58); 3.3413 (1358.67); 3.2752 (0.66); 2.6758 (1.21); 2.6711 (1.86);2.5416 (1.04); 2.5247 (3.14); 2.5068 (206.51); 2.5026 (285.02); 2.4985(203.82); 2.3336 (1.4); 2.3291 (1.76); 2.073 (2.52); 1.9885 (7.71);1.6108 (1.9); 1.5968 (4.8); 1.59 (5.1); 1.5767 (2.1); 1.2799 (0.58);1.2589 (1.23); 1.2344 (1.37); 1.2154 (2.1); 1.2016 (4.33); 1.1931(5.24); 1.1801 (1.87); 1.1748 (4.28); 1.1569 (2.03); 0.8595 (0.42);0.6779 (0.36); −0.0002 (6.05) Ex. 29, solvent: [DMSO], spectrometer:399.95 MHz 11.5012 (3.45); 7.8648 (3.09); 7.8592 (3.49); 7.7164 (1.51);7.7101 (1.37); 7.6943 (2.21); 7.6884 (2.2); 7.6159 (3.95); 7.594 (2.49);4.0557 (0.65); 4.0379 (1.84); 4.0213 (16); 4.0026 (0.71); 3.4274 (0.34);3.3515 (266.05); 3.349 (285.95); 3.3448 (214.54); 3.3422 (330.15);3.3382 (346.98); 3.3349 (418.93); 3.293 (1.7); 3.2756 (1.97); 3.2593(1.38); 3.2431 (0.63); 2.6712 (1.08); 2.6665 (0.8); 2.5414 (0.49);2.5021 (170.74); 2.3288 (1.03); 2.3248 (0.78); 2.0733 (0.83); 1.9886(6.8); 1.9206 (1.12); 1.8997 (3.5); 1.8826 (1.26); 1.5485 (1.15); 1.5306(3.67); 1.5136 (0.94); 1.2328 (0.5); 1.1925 (1.89); 1.1747 (3.72);1.1569 (1.93); 1.121 (14.9); 1.1043 (14.88); −0.0002 (10.09) Ex. 30,solvent: [DMSO], spectrometer: 399.95 MHz 17.8767 (0.49); 16.7278 (0.5);15.2907 (0.46); 14.6922 (0.48); 11.3194 (0.47); 9.9917 (0.45); 9.5478(1.93); 9.4196 (4.84); 7.9522 (1.92); 7.697 (1.24); 7.6759 (1.54);7.6545 (1.48); 7.6289 (0.45); 7.5637 (3.75); 7.5423 (4.82); 7.5163(0.81); 7.4807 (3.23); 7.4748 (3.56); 7.2683 (2.26); 7.2621 (1.93);7.2473 (1.94); 7.24 (1.91); 6.5709 (0.48); 6.1831 (0.45); 4.9061 (1.2);4.8649 (1.59); 4.5294 (1.43); 4.5247 (1.64); 4.4875 (1.39); 4.4825(1.3); 4.4256 (1.93); 4.1384 (0.72); 4.0647 (6.28); 4.0384 (0.58);4.0199 (0.67); 3.9606 (0.54); 3.9181 (0.47); 3.8854 (16); 3.759 (0.48);3.4178 (0.55); 3.3771 (1.43); 3.3282 (1057.25); 3.251 (0.64); 2.8906(12.28); 2.7309 (10.63); 2.6754 (1.93); 2.6707 (2.33); 2.5407 (1.33);2.5057 (285.9); 2.5017 (383.65); 2.4982 (282.92); 2.3283 (2.31); 2.0733(2.62); 1.9883 (1.97); 1.8712 (0.61); 1.7761 (11.28); 1.7311 (4.12);1.6113 (1.99); 1.5966 (6.09); 1.5904 (5.32); 1.5777 (2.22); 1.2931(0.88); 1.279 (1.92); 1.273 (2.06); 1.2578 (0.96); 1.2365 (1.31); 1.2229(1.94); 1.2088 (4.32); 1.2025 (4.5); 1.1879 (1.67); 1.1747 (0.96);1.1567 (0.93); 0.0078 (1.82); −0.0002 (58.33); −0.0086 (1.83); −2.3925(0.46); −2.4975 (0.45); −3.438 (0.46) Ex. 31, solvent: [DMSO],spectrometer: 399.95 MHz 9.6271 (0.33); 9.4864 (1.04); 9.3652 (4.55);7.6886 (0.76); 7.6822 (0.75); 7.5821 (0.72); 7.5605 (1.05); 7.4744(2.86); 7.4687 (2.84); 7.4508 (0.45); 7.4243 (4.62); 7.4029 (5.04);7.3666 (0.94); 7.362 (1.49); 7.3577 (0.73); 7.345 (4.29); 7.341 (2.48);7.3269 (4.69); 7.3153 (1.34); 7.311 (2.53); 7.3074 (1.78); 7.3007(0.69); 7.2937 (2.58); 7.2842 (0.59); 7.2752 (0.73); 7.2699 (0.96);7.2509 (1.5); 7.2417 (3.98); 7.2377 (4.77); 7.2211 (3.59); 7.0343(0.74); 7.0277 (0.66); 7.0153 (0.67); 6.96 (1.73); 6.9536 (1.69); 6.9387(1.64); 6.9318 (1.6); 5.4626 (2.05); 5.4257 (2.49); 4.9216 (1.23);4.9128 (2.37); 4.8762 (2.17); 4.0758 (0.37); 4.0556 (0.88); 4.0379(2.56); 4.0201 (2.74); 4.0023 (0.88); 3.9667 (3.2); 3.9535 (0.34);3.8996 (16); 3.3929 (0.35); 3.3332 (300.56); 3.3257 (628.51); 3.3027(7.43); 2.6752 (1.18); 2.6706 (1.5); 2.6659 (1.01); 2.5407 (0.85); 2.524(2.63); 2.5193 (3.68); 2.5058 (169.66); 2.5016 (233.25); 2.4977(156.25); 2.3329 (1.14); 2.3282 (1.65); 2.3237 (1.1); 2.0733 (1.21);1.9884 (11.36); 1.6066 (1.94); 1.5924 (4.57); 1.5856 (4.63); 1.5728(2.04); 1.2823 (0.53); 1.2698 (0.96); 1.2621 (1.07); 1.2482 (0.71);1.235 (1.64); 1.2116 (1.99); 1.198 (3.98); 1.1921 (7.04); 1.1746 (6.85);1.1567 (3.11); 0.1462 (0.36); 0.0081 (2); −0.0002 (76.87); −0.0085(2.13); −0.1493 (0.33) Ex. 32, solvent: [DMSO], spectrometer: 399.95 MHz19.4883 (0.33); 14.4743 (0.34); 9.9628 (0.33); 9.4772 (1.71); 9.366(4.51); 8.5874 (0.8); 8.5782 (0.78); 8.5563 (2.19); 8.547 (2.12); 7.8384(1.13); 7.8194 (2.22); 7.8147 (2.2); 7.8004 (1.32); 7.7955 (1.32);7.7145 (0.49); 7.6895 (0.9); 7.6743 (0.51); 7.6709 (0.55); 7.5658 (1.2);7.5441 (1.65); 7.5333 (1.55); 7.5212 (3.6); 7.5155 (3.87); 7.4745(3.75); 7.4531 (4.46); 7.4106 (3.5); 7.3909 (2.71); 7.3429 (1.51);7.3315 (1.79); 7.3238 (1.72); 7.3124 (1.73); 7.2885 (0.58); 7.2779(0.44); 7.2717 (2.25); 7.265 (2.21); 7.2499 (1.86); 7.2432 (1.77);7.1046 (0.9); 7.0848 (0.86); 5.296 (1.4); 5.256 (3.53); 5.2123 (3.53);5.1725 (1.5); 4.9686 (2.74); 4.1368 (5.32); 4.0557 (0.94); 4.0379(2.86); 4.0202 (2.95); 3.9976 (16); 3.3915 (0.41); 3.3305 (304.35);3.3279 (296.34); 3.3249 (391.32); 3.2506 (0.34); 2.6708 (1.53); 2.5409(0.84); 2.5016 (246.17); 2.4386 (0.36); 2.4326 (0.43); 2.3282 (1.61);2.0734 (1.6); 1.9885 (11.41); 1.9079 (0.43); 1.6004 (2.1); 1.5867 (5.4);1.5798 (5.52); 1.5671 (2.28); 1.2692 (0.65); 1.2565 (1.56); 1.2491(1.54); 1.235 (1.41); 1.2013 (1.93); 1.192 (5.11); 1.1816 (4.31); 1.1746(6.69); 1.1672 (1.83); 1.1569 (3.02); 0.0075 (2.36); −0.0002 (43.57);−1.8063 (0.33) Ex. 33, solvent: [DMSO], spectrometer: 399.95 MHz 9.5775(4.49); 9.5053 (0.45); 7.7786 (3.6); 7.7682 (0.92); 7.7572 (4.87);7.7138 (0.34); 7.692 (0.35); 7.5946 (0.68); 7.573 (0.96); 4.0552 (0.63);4.0374 (1.94); 4.0273 (2.07); 4.0163 (16); 4.002 (0.93); 3.4947 (0.62);3.4821 (0.65); 3.3765 (615.2); 3.372 (488.62); 3.3684 (526.05); 3.3645(546.77); 3.3625 (654.08); 3.359 (560.12); 3.2239 (0.35); 2.6782 (1.18);2.6736 (1.67); 2.669 (1.25); 2.5438 (0.92); 2.527 (3); 2.5222 (4.56);2.5136 (82.6); 2.5091 (180.41); 2.5045 (246.26); 2.5 (178.36); 2.4955(86.07); 2.3358 (1.2); 2.3312 (1.65); 2.3267 (1.27); 2.2807 (1.71);2.2634 (1.73); 2.2212 (0.46); 2.2023 (0.41); 2.0759 (1.71); 1.9902(8.07); 1.6323 (1.61); 1.6181 (3.95); 1.6112 (4.4); 1.5979 (2.13);1.3975 (0.64); 1.3544 (0.4); 1.2986 (2.04); 1.2849 (4.05); 1.2782(4.47); 1.2636 (1.91); 1.2528 (0.8); 1.2356 (1.05); 1.1924 (2.24);1.1746 (4.33); 1.1568 (2.15); 1.0046 (0.45); 0.9858 (0.8); 0.967 (0.39);0.9035 (4.02); 0.8858 (8.59); 0.8681 (3.9); 0.008 (0.47); −0.0002(15.07); −0.0086 (0.55) Ex. 34, solvent: [DMSO], spectrometer: 601.6 MHz11.5357 (2.35); 9.5094 (2.93); 7.7744 (2.41); 7.7701 (2.69); 7.7094(1.22); 7.7051 (1.07); 7.6949 (1.54); 7.6906 (1.44); 7.5923 (2.62);7.5777 (2.13); 4.3468 (0.77); 4.3348 (2.43); 4.3228 (2.45); 4.3107(0.79); 4.0465 (1.21); 4.0346 (3.71); 4.0228 (3.71); 4.011 (1.24);3.3485 (39.29); 3.063 (1.4); 2.8638 (1.42); 2.5098 (6.24); 2.5069(13.35); 2.5039 (18.23); 2.5009 (13.5); 2.498 (6.41); 1.991 (16); 1.6057(1.04); 1.5963 (2.46); 1.5918 (2.7); 1.5829 (1.07); 1.4232 (3.53);1.4112 (7.51); 1.3991 (3.52); 1.3831 (0.35); 1.371 (0.73); 1.359 (0.33);1.2704 (1.14); 1.2612 (2.43); 1.2568 (2.67); 1.2472 (1); 1.1869 (4.33);1.175 (8.76); 1.1632 (4.27); −0.0002 (1.62) Ex. 35, solvent: [DMSO],spectrometer: 399.95 MHz 11.5005 (4.87); 9.4951 (6.27); 7.7618 (4.81);7.7554 (5.95); 7.7144 (2.63); 7.7078 (2); 7.6925 (3.37); 7.686 (2.85);7.5904 (5.35); 7.5686 (3.92); 4.2725 (3.11); 4.2554 (6.27); 4.2381(3.15); 4.0382 (0.36); 4.0188 (0.33); 3.4841 (0.32); 3.4614 (0.46);3.4443 (0.55); 3.4137 (0.86); 3.3433 (1492.06); 3.2822 (3.03); 3.25(1.84); 3.2136 (1.16); 3.1836 (0.68); 3.1568 (0.48); 3.0604 (1.58);2.8553 (1.58); 2.6765 (0.88); 2.6715 (1.15); 2.6668 (0.89); 2.5808(0.37); 2.5419 (0.94); 2.5068 (140.47); 2.5027 (192.83); 2.4986(142.05); 2.4395 (1.46); 2.4062 (0.88); 2.4024 (0.84); 2.3507 (0.48);2.3295 (1.39); 2.3251 (1.13); 2.3016 (0.38); 2.0748 (2.08); 1.9892(1.51); 1.8724 (0.6); 1.8543 (2.3); 1.8363 (4.51); 1.8184 (4.61); 1.8002(2.47); 1.7815 (0.63); 1.6082 (2.21); 1.5942 (5.23); 1.5868 (5.61);1.5738 (2.55); 1.5334 (0.32); 1.3974 (9.15); 1.2748 (2.5); 1.2617(5.29); 1.2545 (5.68); 1.24 (2.34); 1.1923 (0.45); 1.1741 (0.77); 1.1568(0.42); 0.8614 (7.69); 0.8431 (16); 0.8244 (7.18); −0.0002 (12.56);−0.0087 (0.62) Ex. 36, solvent: [DMSO], spectrometer: 601.6 MHz 11.4548(1.5); 9.3583 (1.27); 7.9479 (0.56); 7.9434 (0.64); 7.9378 (0.61);7.9332 (0.58); 7.7878 (0.37); 7.7856 (0.39); 7.7807 (0.35); 7.7778(0.36); 7.7728 (0.41); 7.771 (0.4); 7.4149 (0.55); 7.3992 (0.89); 7.3837(0.52); 4.2745 (0.87); 4.2629 (1.71); 4.2513 (0.87); 4.0461 (1.23);4.0343 (3.73); 4.0224 (3.73); 4.0106 (1.24); 3.3508 (5.32); 3.0615(0.46); 2.857 (0.46); 2.5216 (0.38); 2.5067 (18.22); 2.5038 (24.1);2.5008 (17.69); 1.9909 (16); 1.8508 (0.62); 1.8388 (1.21); 1.8269(1.23); 1.8149 (0.65); 1.5953 (0.63); 1.5859 (1.53); 1.5813 (1.8);1.5724 (0.68); 1.2932 (0.72); 1.2841 (1.56); 1.2796 (1.68); 1.2702(0.7); 1.1866 (4.25); 1.1747 (8.49); 1.1629 (4.18); 0.9297 (0.46);0.8596 (1.94); 0.8473 (4.1); 0.835 (1.9); 0.8263 (0.36); −0.0002 (1.87)Ex. 37, solvent: [DMSO], spectrometer: 399.95 MHz 11.4582 (4.4); 9.3437(3.47); 7.9546 (1.99); 7.9477 (2.21); 7.9391 (2.06); 7.9323 (2.22);7.7969 (1.11); 7.7896 (1.15); 7.7858 (1.31); 7.7786 (1.09); 7.7744(1.19); 7.7674 (1.35); 7.7633 (1.35); 7.7565 (1.05); 7.4195 (2.16);7.3953 (2.98); 7.3726 (1.97); 4.4209 (0.48); 4.402 (0.49); 4.3576(1.39); 4.3397 (4.42); 4.3215 (4.47); 4.3031 (1.4); 4.2264 (0.44); 4.209(0.72); 4.1911 (0.99); 4.1728 (0.68); 4.0554 (1.12); 4.0376 (3.61);4.0198 (3.61); 4.002 (1.17); 3.4598 (0.4); 3.3366 (26.64); 3.2408(0.63); 3.2327 (0.6); 3.18 (0.49); 3.0617 (7.35); 2.9068 (0.33); 2.862(7.44); 2.6758 (0.84); 2.6713 (1.17); 2.6666 (0.87); 2.5416 (0.6);2.5245 (2.07); 2.5199 (2.85); 2.5063 (123.98); 2.5022 (170.52); 2.4985(114.01); 2.3384 (0.38); 2.3333 (0.8); 2.3286 (1.21); 2.3245 (0.85);2.3194 (0.49); 2.0755 (0.47); 1.9893 (16); 1.9091 (0.6); 1.5982 (1.91);1.5841 (4.44); 1.5769 (4.72); 1.5638 (2.26); 1.4339 (6.76); 1.4158(15.95); 1.3976 (7.06); 1.3891 (2.15); 1.3757 (2.45); 1.371 (4.02);1.3576 (1.14); 1.3528 (1.86); 1.2979 (2.59); 1.2842 (4.49); 1.2773(4.85); 1.2627 (2.22); 1.2354 (0.95); 1.1923 (4.5); 1.1745 (8.88);1.1567 (4.35); 0.8883 (0.35); 0.008 (0.92); −0.0002 (35.96); −0.0085(1.05) Ex. 38, solvent: [DMSO], spectrometer: 601.6 MHz 9.5496 (0.57);9.4141 (0.99); 7.9531 (2.11); 7.6736 (0.9); 7.6699 (0.6); 7.6588 (0.63);7.5771 (0.34); 7.5534 (0.98); 7.5391 (1.1); 7.433 (0.87); 7.4286 (0.92);7.2912 (0.53); 7.2868 (0.49); 7.2769 (0.48); 7.2725 (0.45); 4.3763(0.46); 4.3643 (0.47); 4.2607 (0.37); 4.1747 (0.32); 4.1628 (0.38);3.4447 (5.41); 3.3584 (170.61); 3.335 (1.41); 3.2387 (2.83); 2.8911(16); 2.7312 (13.04); 2.7307 (12.77); 2.5251 (0.36); 2.522 (0.46);2.5189 (0.48); 2.5099 (12.87); 2.507 (27.63); 2.504 (37.72); 2.501(27.87); 2.4981 (13.11); 1.6046 (0.84); 1.6005 (0.7); 1.5953 (0.94);1.5911 (1.16); 1.5824 (0.42); 1.4525 (0.74); 1.4405 (1.57); 1.4285(0.74); 1.308 (1.26); 1.296 (2.69); 1.2908 (0.39); 1.284 (1.46); 1.2771(0.59); 1.1964 (0.45); 1.1876 (0.87); 1.1835 (0.88); 1.1744 (0.48);−0.0002 (5.92) Ex. 39, solvent: [DMSO], spectrometer: 399.95 MHz 16.4832(0.33); 15.8688 (0.33); 13.2954 (0.33); 9.6257 (0.34); 9.6097 (2.28);9.4715 (4.25); 9.4357 (0.37); 9.3286 (0.34); 8.0115 (1.98); 8.0058(2.14); 7.6392 (4.36); 7.6335 (3.82); 7.6013 (0.4); 7.5949 (0.44);7.5777 (0.47); 7.5615 (0.48); 7.5253 (0.37); 7.4896 (3.22); 7.4834(3.02); 7.4395 (0.43); 7.4325 (0.57); 7.4255 (0.52); 7.4196 (0.37);5.7522 (0.33); 4.1774 (0.4); 4.1601 (0.99); 4.1421 (1.31); 4.1253(1.47); 4.1073 (1.28); 4.0847 (8.62); 4.0554 (1.29); 4.0376 (3.86);4.0199 (3.78); 4.0022 (1.25); 3.9064 (0.38); 3.8793 (1.92); 3.8664(14.52); 3.8554 (1.87); 3.8367 (0.71); 3.8182 (1.21); 3.8004 (1.64);3.7833 (1.43); 3.7657 (1.14); 3.7471 (0.43); 3.7013 (0.51); 3.6822(0.73); 3.6642 (0.9); 3.6454 (1); 3.6338 (0.83); 3.6158 (0.91); 3.5968(0.64); 3.5781 (0.38); 3.4622 (0.34); 3.4401 (0.39); 3.4079 (0.75);3.3466 (768.76); 3.3431 (1758.18); 3.3199 (5.3); 3.2876 (0.84); 3.2746(0.59); 3.2684 (0.52); 3.2291 (0.35); 3.2188 (0.44); 2.6767 (1.39);2.6717 (1.92); 2.6678 (1.4); 2.5418 (0.89); 2.5252 (3.39); 2.5111(113.97); 2.5071 (219.12); 2.5029 (302.49); 2.4987 (211.86); 2.4946(105.8); 2.4557 (0.43); 2.3342 (1.35); 2.3295 (1.8); 2.3249 (1.43);2.075 (2.09); 1.9893 (16); 1.6178 (2.02); 1.6037 (6.07); 1.5977 (5.35);1.5842 (2.19); 1.5755 (0.39); 1.3835 (0.33); 1.3449 (0.36); 1.3127(1.03); 1.298 (2.27); 1.2915 (2.11); 1.2761 (0.89); 1.2588 (0.57);1.2327 (3.01); 1.2191 (4.19); 1.2121 (4.3); 1.1979 (1.6); 1.1924 (4.68);1.1746 (8.79); 1.1567 (8.3); 1.1383 (9.27); 1.1204 (4.08); 1.0992(0.35); 0.9885 (0.33); 0.9703 (2.29); 0.9523 (4.58); 0.9345 (2.19);−0.0002 (11.63); −0.0088 (0.43); −3.0168 (0.32) Ex. 40, solvent: [DMSO],spectrometer: 399.95 MHz 11.491 (2.41); 7.8981 (2.63); 7.8918 (2.76);7.7092 (1.29); 7.7028 (1.18); 7.6873 (1.79); 7.6809 (1.74); 7.5849(3.2); 7.563 (2.31); 4.056 (0.73); 4.0381 (2.56); 4.0288 (11.26); 4.0205(2.67); 4.0026 (0.76); 3.3518 (0.45); 3.3286 (152.33); 2.5244 (1.09);2.5195 (1.69); 2.5109 (19.1); 2.5065 (38.19); 2.502 (49.79); 2.4974(35.73); 2.493 (17.31); 2.3955 (16); 2.3286 (0.34); 2.074 (0.42); 1.9888(9.22); 1.8766 (1.77); 1.6065 (0.84); 1.1926 (2.46); 1.1748 (4.87);1.157 (2.4); −0.0002 (5.14) Ex. 41, solvent: [DMSO], spectrometer: 601.6MHz 9.4121 (0.42); 7.9528 (1.18); 7.7388 (0.36); 7.7028 (0.82); 7.6882(1.07); 7.674 (0.37); 7.6583 (0.38); 7.6479 (0.99); 7.6438 (1.12);7.6126 (1.11); 7.5995 (1.46); 7.5769 (0.36); 7.5533 (0.48); 7.5395(0.48); 7.433 (0.5); 7.4291 (0.53); 7.3221 (0.64); 7.2903 (0.44); 7.2761(0.33); 7.2716 (0.34); 4.3716 (1.39); 4.3595 (1.67); 4.272 (0.39);4.2601 (0.39); 4.2481 (0.36); 4.1277 (0.42); 4.1191 (0.42); 4.0334(0.56); 4.0216 (0.56); 3.5061 (0.42); 3.4808 (1.12); 3.4549 (16); 3.444(2.94); 3.4284 (0.6); 3.3956 (1.34); 3.3758 (5.24); 3.3517 (4904.54);3.3282 (80.11); 3.2755 (1.57); 3.2474 (4.78); 3.2383 (1.31); 3.1704(1.74); 3.1617 (1.71); 3.1108 (1.82); 3.0743 (1.14); 2.8906 (8.65);2.8645 (4.58); 2.7306 (7.07); 2.618 (10.41); 2.615 (14.06); 2.6121(10.4); 2.5428 (5.84); 2.5243 (20.27); 2.5213 (25.42); 2.5182 (25.36);2.5091 (738.32); 2.5062 (1554.79); 2.5033 (2093.86); 2.5003 (1556.28);2.4974 (750.49); 2.3904 (9.64); 2.3874 (13.16); 2.3845 (9.61); 2.283(0.4); 2.0787 (15.29); 1.9906 (2.25); 1.6777 (3.23); 1.6044 (0.51);1.591 (0.77); 1.582 (0.49); 1.5066 (0.63); 1.4948 (0.86); 1.4825 (0.67);1.4514 (2.04); 1.4394 (4.05); 1.4273 (2.94); 1.415 (1.05); 1.3496(2.36); 1.3072 (1.28); 1.2954 (1.78); 1.2833 (1.18); 1.2666 (0.69);1.2576 (1.03); 1.2338 (6.68); 1.1951 (0.48); 1.1859 (1.2); 1.174 (1.49);1.1622 (0.72); 1.0541 (0.42); 0.8646 (0.43); 0.8535 (1.03); 0.8416(0.52); 0.0965 (1.89); 0.0052 (14.67); −0.0002 (473.67); −0.0057(19.93); −0.1 (1.92) Ex. 42, solvent: [DMSO], spectrometer: 601.6 MHz11.0933 (3.12); 10.6126 (0.51); 9.5132 (3.58); 9.5027 (0.8); 7.8641(2.73); 7.86 (2.86); 7.8428 (1.09); 7.839 (0.51); 7.8313 (0.4); 7.7552(1.31); 7.751 (1.2); 7.7406 (1.56); 7.7365 (1.44); 7.5785 (3.5); 7.564(2.35); 7.5578 (0.51); 7.5418 (0.41); 4.1945 (2.61); 4.0334 (0.76);4.0215 (0.81); 4.0064 (12.33); 3.3813 (1.49); 3.3561 (1038.24); 3.3325(10.5); 2.6153 (1.84); 2.543 (0.72); 2.5245 (2.78); 2.5214 (3.59);2.5181 (4.4); 2.5063 (218.81); 2.5036 (275.25); 2.3877 (1.67); 2.2932(0.59); 2.2827 (16); 2.0785 (0.51); 1.9907 (3.1); 1.6109 (1.37); 1.6016(3.69); 1.5971 (3.87); 1.5881 (1.44); 1.2646 (1.41); 1.2554 (3.39);1.2511 (3.52); 1.2413 (1.86); 1.2344 (0.88); 1.1859 (0.82); 1.1741(1.59); 1.1622 (0.81); 0.0049 (1.62); −0.0002 (30.57) Ex. 43, solvent:[DMSO], spectrometer: 601.6 MHz 9.5611 (2.61); 9.4204 (5.99); 7.6917(2.08); 7.6775 (2.5); 7.644 (2.35); 7.6398 (2.43); 7.5687 (5.27); 7.5544(5.96); 7.5008 (1.35); 7.4967 (1.29); 7.4867 (1.16); 7.4825 (1.15);7.4199 (4.23); 7.4158 (4.42); 7.2921 (2.65); 7.288 (2.5); 7.2779 (2.46);7.2736 (2.33); 4.3914 (0.77); 4.3788 (2.21); 4.367 (2.26); 4.3549(0.78); 4.268 (0.45); 4.2567 (1.31); 4.2449 (1.84); 4.2335 (2.3); 4.2217(1.95); 4.21 (0.64); 4.1658 (0.64); 4.1541 (1.99); 4.1423 (2.5); 4.1343(1.96); 4.1311 (2.19); 4.1224 (2.3); 4.1193 (1.88); 4.1114 (2.32);4.0996 (1.8); 4.0878 (0.56); 4.0334 (0.37); 4.0216 (0.36); 3.7795(0.53); 3.7678 (1.63); 3.7559 (2.07); 3.7448 (1.99); 3.7328 (1.56);3.7214 (0.53); 3.6918 (0.56); 3.68 (0.78); 3.6676 (0.94); 3.6558 (0.78);3.5796 (0.83); 3.5678 (1); 3.5556 (0.85); 3.5436 (0.6); 3.4046 (0.45);3.3945 (1.21); 3.3858 (1.16); 3.3796 (1.18); 3.3518 (1984.37); 3.3279(16.06); 3.3028 (0.46); 3.1702 (0.33); 3.1616 (0.43); 2.6179 (4.37);2.6151 (5.71); 2.6123 (4.23); 2.5427 (2.81); 2.5332 (0.94); 2.5242(9.59); 2.5211 (13.27); 2.5179 (16.58); 2.5062 (657.61); 2.5033(846.44); 2.5005 (615.2); 2.4784 (2.21); 2.3903 (3.99); 2.3875 (5.24);2.3847 (3.83); 2.0787 (4.37); 1.9906 (1.25); 1.6177 (1.12); 1.6056(4.24); 1.5967 (6.28); 1.5925 (6.54); 1.5838 (2.53); 1.4508 (3.21);1.4388 (6.55); 1.4268 (3.06); 1.306 (7.37); 1.2941 (16); 1.282 (9.65);1.2721 (1.16); 1.2576 (0.69); 1.2338 (3.09); 1.2054 (2.8); 1.1965(5.73); 1.1922 (5.97); 1.183 (2.39); 1.1741 (0.91); 1.1621 (0.47);1.1436 (6.79); 1.1317 (13.97); 1.1198 (6.51); 0.9438 (2.6); 0.932(5.36); 0.9202 (2.47); 0.8535 (0.4); 0.0967 (0.49); 0.005 (5.69);−0.0002 (104.53); −0.0999 (0.47) Ex. 44, solvent: [DMSO], spectrometer:601.6 MHz 9.4685 (3.13); 7.6186 (2.15); 7.6043 (2.37); 7.5156 (2.09);7.5118 (2.18); 7.3065 (1.24); 7.3024 (1.24); 7.2923 (1.16); 7.2882(1.12); 5.2573 (1.78); 5.2279 (2.2); 4.9892 (2.11); 4.9598 (1.74);4.0648 (0.9); 4.0453 (1.36); 4.0335 (3.87); 4.0217 (3.86); 4.0098(1.32); 3.9354 (10.54); 3.4336 (0.7); 3.3766 (1.21); 3.352 (365.17);3.3252 (0.47); 2.6151 (0.96); 2.5429 (0.42); 2.5034 (150.98); 2.3876(0.93); 1.9907 (16); 1.6188 (1.49); 1.6097 (3.52); 1.6054 (3.55); 1.5965(1.28); 1.2734 (0.4); 1.2338 (0.67); 1.217 (1.28); 1.2079 (2.97); 1.2038(3.11); 1.1942 (1.13); 1.186 (4.37); 1.1742 (8.34); 1.1623 (4.17);−0.0002 (1.27) Ex. 45, solvent: [DMSO], spectrometer: 399.95 MHz 11.5629(3.17); 9.5197 (3.89); 7.8939 (0.68); 7.8145 (2.97); 7.8081 (3.34);7.6813 (1.42); 7.675 (1.32); 7.6594 (2.05); 7.653 (2.01); 7.5849 (4.03);7.563 (2.7); 7.5353 (0.32); 5.7625 (0.52); 4.1942 (1); 4.1104 (12.73);4.0549 (0.57); 4.0371 (1.62); 4.0193 (1.67); 4.0016 (0.65); 3.3488(381.8); 3.3413 (634.34); 3.0337 (16); 2.681 (0.92); 2.6766 (1.94);2.672 (2.7); 2.6675 (1.97); 2.5421 (1.6); 2.5254 (4.95); 2.5207 (7.26);2.512 (132.84); 2.5075 (285.73); 2.503 (383.95); 2.4984 (271.1); 2.4939(125.41); 2.3389 (0.83); 2.3343 (1.83); 2.3297 (2.55); 2.3251 (1.84);2.0772 (0.62); 1.99 (7.2); 1.612 (1.36); 1.5977 (3.37); 1.5909 (3.47);1.5778 (1.53); 1.2731 (1.73); 1.2596 (3.49); 1.2529 (3.76); 1.2378(2.87); 1.1921 (1.91); 1.1742 (3.78); 1.1565 (1.84); 0.8539 (0.37);0.008 (1.19); −0.0002 (35.07); −0.0077 (1.04) Ex. 45, solvent: [DMSO],spectrometer: 399.95 MHz 11.5617 (2.61); 9.5199 (2.8); 7.8135 (2.59);7.8072 (2.92); 7.6806 (1); 7.6741 (0.94); 7.6586 (1.53); 7.6522 (1.56);7.5846 (2.73); 7.5627 (1.8); 4.1102 (12.24); 4.0369 (0.87); 4.0191(0.88); 4.0016 (0.61); 3.3499 (1797.52); 3.2245 (0.46); 3.033 (16);2.6813 (0.63); 2.6767 (1.35); 2.6721 (1.89); 2.6675 (1.39); 2.6629(0.67); 2.5424 (1.08); 2.5255 (3.44); 2.5208 (5.1); 2.5121 (94.77);2.5076 (206.74); 2.503 (279.76); 2.4984 (197.63); 2.4939 (91.37); 2.3389(0.58); 2.3343 (1.29); 2.3297 (1.81); 2.3252 (1.31); 2.0765 (2.83);1.9898 (4.26); 1.6115 (1.29); 1.5972 (2.98); 1.5904 (3.18); 1.5772(1.42); 1.273 (1.66); 1.2592 (3.23); 1.2526 (3.51); 1.2379 (1.98); 1.192(1.13); 1.1742 (2.25); 1.1564 (1.08); −0.0002 (8.57) Ex. 46, solvent:[DMSO], spectrometer: 399.95 MHz 9.5373 (0.47); 9.3983 (0.81); 7.7053(0.41); 7.6838 (0.63); 7.6757 (0.42); 7.6635 (0.45); 7.6546 (0.75);7.6313 (0.77); 7.6092 (1.26); 7.5886 (1.33); 7.5792 (0.79); 7.5486(0.9); 7.527 (0.97); 7.4347 (0.79); 7.4282 (0.89); 7.3883 (0.47); 7.3078(1.04); 7.2891 (0.66); 7.2824 (0.56); 7.2677 (0.47); 7.2612 (0.45);4.2924 (1.02); 4.2751 (0.9); 4.182 (0.47); 4.1649 (0.51); 4.1476 (0.56);4.1292 (0.35); 4.0547 (1.37); 4.0369 (3.7); 4.0191 (3.74); 4.0013(1.31); 3.4557 (10.09); 3.4453 (5.02); 3.3427 (771.28); 3.319 (13.1);3.2679 (1.37); 3.2419 (3.06); 3.2325 (2.72); 3.1112 (1.16); 3.072(0.85); 2.8904 (0.43); 2.8646 (2.78); 2.7312 (0.35); 2.6764 (1.44);2.6718 (2); 2.6673 (1.53); 2.5422 (1.53); 2.5253 (3.59); 2.5205 (5.22);2.5117 (95.58); 2.5073 (207.41); 2.5028 (281.65); 2.4982 (204.86);2.4938 (99.47); 2.334 (1.35); 2.3295 (1.9); 2.325 (1.43); 2.0769 (2.16);1.9899 (16); 1.9015 (0.53); 1.8832 (1); 1.8655 (1.18); 1.847 (0.97);1.8267 (0.75); 1.8103 (0.56); 1.7924 (0.52); 1.7738 (0.52); 1.6767(2.49); 1.6439 (0.6); 1.6192 (0.38); 1.5969 (1.32); 1.5899 (1.04);1.5768 (0.52); 1.4012 (0.6); 1.2967 (0.71); 1.2823 (0.75); 1.2755(0.81); 1.258 (0.71); 1.2347 (1.66); 1.2004 (0.58); 1.192 (4.72); 1.1743(9.08); 1.1564 (4.38); 0.8945 (1.45); 0.876 (3.76); 0.8567 (3.53);0.8335 (2.44); 0.8148 (2.63); 0.7962 (1.13); 0.146 (0.39); 0.008 (2.78);−0.0002 (90.84); −0.0085 (3.33); −0.1499 (0.34) Ex. 47, solvent: [DMSO],spectrometer: 601.6 MHz 7.6521 (0.53); 7.4488 (0.87); 7.4092 (0.79);7.3946 (0.85); 7.3798 (0.87); 4.3079 (0.35); 4.2962 (0.64); 4.2842(0.81); 4.2717 (0.82); 4.2604 (0.93); 4.2489 (1.03); 4.2369 (0.57);4.1612 (0.58); 4.1506 (0.59); 4.1386 (0.49); 4.127 (0.54); 4.1149(0.59); 4.1037 (0.33); 4.0456 (0.57); 4.0338 (1.71); 4.022 (1.73);4.0101 (0.58); 3.4532 (16); 3.4036 (1.29); 3.3797 (0.39); 3.3536(287.87); 3.33 (4.06); 3.2402 (1.45); 3.1042 (0.53); 3.095 (0.47);3.0631 (0.57); 2.9405 (0.67); 2.6832 (2.06); 2.6186 (0.56); 2.6157(0.74); 2.6128 (0.54); 2.5249 (1.23); 2.5218 (1.83); 2.5069 (84.85);2.504 (111.28); 2.501 (80.94); 2.391 (0.55); 2.3881 (0.73); 2.3852(0.53); 1.9909 (7.37); 1.8792 (0.58); 1.8669 (0.68); 1.8549 (0.61);1.8371 (0.59); 1.7449 (0.46); 1.7341 (0.59); 1.7232 (0.61); 1.7109(0.61); 1.6979 (0.68); 1.686 (0.86); 1.6637 (1.33); 1.4754 (0.37);1.3882 (0.95); 1.2578 (0.37); 1.2343 (1.25); 1.1862 (2.13); 1.1744(4.02); 1.1625 (2.03); 0.8889 (1.11); 0.8766 (2.26); 0.8638 (2.34);0.8493 (3.1); 0.6607 (0.53); 0.6484 (1.06); 0.6361 (0.51); 0.0051(1.29); −0.0002 (25.89); −0.0056 (0.98) Ex. 48, solvent: [DMSO],spectrometer: 601.6 MHz 7.6625 (0.59); 7.6566 (0.58); 7.6531 (0.62);7.441 (0.93); 7.4125 (0.97); 7.3978 (1.05); 4.3751 (0.97); 4.3634 (1.3);4.3523 (1.07); 4.3412 (1.13); 4.3294 (0.96); 4.3177 (0.36); 4.2724(0.53); 4.0335 (0.92); 4.0217 (0.91); 3.4526 (16); 3.3768 (0.53); 3.3522(580.58); 3.3286 (7.62); 3.2446 (1.32); 3.1036 (0.51); 3.0656 (0.51);2.9399 (0.7); 2.6805 (2.05); 2.6182 (1.09); 2.6153 (1.49); 2.6123 (1.1);2.543 (0.62); 2.5245 (2.25); 2.5215 (3.05); 2.5183 (3.8); 2.5094(79.16); 2.5065 (164.86); 2.5035 (221.76); 2.5005 (162.52); 2.4977(78.12); 2.3906 (1.05); 2.3877 (1.43); 2.3847 (1.05); 2.0789 (0.5);1.9907 (3.97); 1.9066 (0.38); 1.6608 (1.13); 1.4749 (0.38); 1.4506(0.98); 1.4387 (1.81); 1.4266 (1.1); 1.3791 (0.88); 1.3467 (2.94);1.2977 (0.44); 1.2577 (0.56); 1.2337 (1.42); 1.186 (1.28); 1.1742(2.31); 1.1623 (1.19); 0.0052 (2.55); −0.0002 (61.56); −0.0057 (2.57)Ex. 49, solvent: [DMSO], spectrometer: 399.95 MHz 11.3656 (3.86); 9.5142(4.4); 7.7755 (3.59); 7.7692 (3.97); 7.6847 (1.75); 7.6783 (1.49);7.6628 (2.52); 7.6564 (2.33); 7.5817 (4.49); 7.5599 (3.05); 4.0562(1.15); 4.0384 (3.4); 4.0206 (3.6); 4.0034 (16); 3.3453 (94.9); 3.3448(94.73); 3.3197 (17.97); 2.5245 (0.51); 2.511 (7.72); 2.5068 (14.99);2.5023 (19.26); 2.4978 (13.84); 2.4937 (6.76); 2.0729 (0.59); 1.9887(13.71); 1.6091 (1.56); 1.5949 (3.86); 1.588 (4.03); 1.5747 (1.73);1.277 (1.86); 1.2635 (3.82); 1.2568 (4.07); 1.2422 (1.5); 1.1928 (3.82);1.1749 (7.49); 1.1572 (3.7) Ex. 50, solvent: [DMSO], spectrometer: 601.6MHz 9.5618 (2.56); 9.4177 (6.18); 7.9529 (0.98); 7.6923 (2.28); 7.6781(2.69); 7.635 (2.45); 7.6308 (2.6); 7.5617 (5.97); 7.5475 (6.73); 7.5004(1.4); 7.4963 (1.31); 7.4863 (1.23); 7.482 (1.22); 7.4233 (4.05); 7.4191(4.25); 7.2874 (2.63); 7.283 (2.53); 7.2731 (2.42); 7.2688 (2.31);4.3107 (0.81); 4.3036 (0.87); 4.2993 (1.52); 4.2921 (1.53); 4.2806(0.81); 4.1677 (0.49); 4.1596 (1.05); 4.1559 (1.81); 4.1474 (2.05);4.144 (2.45); 4.1362 (2.11); 4.1329 (2.74); 4.1249 (2.63); 4.1211(2.27); 4.1128 (1.37); 4.0421 (1.16); 4.0323 (1.53); 4.0297 (1.5);4.0196 (1.98); 4.0097 (1.08); 4.0068 (1.07); 3.9968 (0.83); 3.7605(0.48); 3.7486 (1.68); 3.7369 (2.16); 3.7256 (2.07); 3.7139 (1.61);3.7018 (0.54); 3.6876 (0.53); 3.6756 (0.76); 3.6634 (0.93); 3.6514(0.75); 3.5736 (0.78); 3.5616 (0.93); 3.5493 (0.81); 3.5373 (0.58);3.4009 (0.71); 3.3887 (0.8); 3.3806 (1.37); 3.3578 (1317.4); 3.334(5.83); 2.8908 (7.36); 2.7308 (5.98); 2.6185 (1.57); 2.6155 (2.16);2.6126 (1.59); 2.5433 (0.92); 2.5248 (3.01); 2.5217 (4.1); 2.5186(4.76); 2.5095 (118.16); 2.5067 (245.74); 2.5038 (330.23); 2.5009(240.75); 2.4981 (114.58); 2.3909 (1.49); 2.3879 (2.06); 2.385 (1.48);2.0787 (0.93); 1.8893 (1); 1.8773 (2.04); 1.8652 (2.07); 1.8532 (1.07);1.8217 (0.59); 1.8094 (1.15); 1.7977 (1.5); 1.7863 (1.74); 1.7743(1.53); 1.7621 (0.74); 1.6799 (0.65); 1.6676 (1.17); 1.6574 (1.68);1.645 (1.65); 1.6348 (1.13); 1.6225 (0.67); 1.6179 (1.23); 1.6084(4.94); 1.6039 (3.6); 1.5991 (6.24); 1.5947 (7.45); 1.5859 (2.64);1.2954 (1.19); 1.2863 (2.43); 1.2819 (2.67); 1.2724 (1); 1.2578 (0.42);1.2335 (1.57); 1.2037 (2.86); 1.1947 (5.93); 1.1903 (6.34); 1.181(2.45); 1.1407 (7.11); 1.1288 (14.87); 1.1168 (6.89); 0.9415 (2.6);0.9297 (5.46); 0.9179 (2.57); 0.8865 (3.17); 0.8743 (6.67); 0.862(3.13); 0.8535 (0.38); 0.8172 (7.63); 0.8049 (16); 0.7926 (7.21); 0.0051(1.34); −0.0002 (32.06); −0.0057 (1.19) Ex. 51, solvent: [DMSO],spectrometer: 601.6 MHz 11.2435 (1); 9.3497 (0.74); 7.9531 (0.39);7.7736 (0.6); 7.7601 (0.7); 7.7304 (2.91); 7.7161 (3.31); 7.6522 (3.79);7.6386 (3.74); 7.6244 (3.53); 7.5889 (2.65); 7.5753 (2.41); 7.5207(1.21); 7.4121 (11.62); 7.4027 (3.64); 7.3862 (2.56); 7.3118 (2.15);7.2988 (1.8); 7.2009 (0.39); 6.8169 (0.48); 4.3007 (3.14); 4.2901 (3.3);4.2794 (2.58); 4.2566 (2.26); 4.2028 (1.63); 4.1284 (3.82); 4.1178(3.61); 4.107 (3.02); 4.0674 (1.32); 4.055 (1.55); 4.0456 (2.7); 4.0338(4.82); 4.022 (4.4); 4.0102 (1.78); 3.9587 (1.64); 3.947 (2.06); 3.9353(1.89); 3.9165 (1.96); 3.9041 (2.3); 3.8933 (1.94); 3.8468 (1.72);3.7093 (1.04); 3.6044 (0.96); 3.3585 (2804.89); 3.3349 (16.31); 3.2711(0.92); 3.2466 (0.88); 3.1423 (0.68); 3.0944 (0.54); 3.061 (1.47);3.0465 (1.27); 2.9693 (1.33); 2.8912 (2.99); 2.8563 (1.82); 2.8399(3.68); 2.8293 (3.66); 2.7312 (2.47); 2.6188 (3.62); 2.616 (4.79);2.6132 (3.59); 2.5436 (1.95); 2.525 (9.26); 2.522 (12.69); 2.5186(16.24); 2.507 (555.84); 2.5043 (726.37); 2.5015 (536.53); 2.3912(3.62); 2.3884 (4.75); 2.3856 (3.53); 2.2958 (0.37); 2.2837 (0.81);2.2716 (0.33); 2.0789 (2.13); 1.991 (15.17); 1.8862 (1.72); 1.8744(3.51); 1.8624 (4.2); 1.8509 (3.63); 1.8425 (3.66); 1.8307 (3.67);1.8188 (3.58); 1.8066 (2.89); 1.794 (2.27); 1.7812 (2.03); 1.7642(2.22); 1.7173 (14.52); 1.6892 (3.36); 1.6419 (1.13); 1.5709 (1.75);1.5668 (1.84); 1.5023 (3.27); 1.4837 (3.07); 1.374 (3.95); 1.3622(2.97); 1.3502 (2.21); 1.3334 (3.83); 1.3217 (5.49); 1.3103 (4.13);1.2978 (3.26); 1.2679 (4.55); 1.2579 (5.13); 1.2343 (9.67); 1.1974(3.99); 1.1862 (10.63); 1.1743 (14.27); 1.1624 (12.11); 1.1558 (13.88);1.1412 (16); 1.1295 (8.23); 1.1049 (6.61); 1.0708 (6); 1.0599 (8.58);0.9401 (3.69); 0.9284 (5.1); 0.9172 (2.68); 0.8835 (5.11); 0.8713(10.54); 0.865 (6.44); 0.8588 (10.32); 0.8536 (8.8); 0.845 (12.86);0.8317 (12.07); 0.78 (1.98); 0.7676 (0.91); 0.0966 (0.62); 0.005 (6.46);−0.0002 (127.14); −0.0055 (5.46); −0.1 (0.6) Ex. 52, solvent: [DMSO],spectrometer: 399.95 MHz 9.4063 (0.33); 7.7318 (0.72); 7.7103 (0.89);7.6897 (0.37); 7.6725 (0.36); 7.6593 (1.1); 7.6531 (1.26); 7.6406(1.06); 7.6247 (0.89); 7.5947 (0.61); 7.5698 (0.76); 7.5483 (0.56);7.5048 (0.39); 7.4401 (0.74); 7.4106 (1.09); 7.3918 (1.37); 7.2958(0.47); 7.2895 (0.56); 7.2747 (0.49); 7.2686 (0.49); 4.4001 (0.35);4.3823 (1.01); 4.3643 (1.22); 4.2654 (0.77); 4.2473 (0.94); 4.2311(0.91); 4.2129 (0.73); 4.1602 (0.44); 4.147 (0.55); 4.1419 (0.6); 4.1332(0.55); 4.1246 (0.64); 4.1084 (0.36); 4.055 (1.34); 4.0461 (0.4); 4.0372(3.72); 4.0282 (0.46); 4.0194 (3.81); 4.0016 (1.44); 3.9349 (0.82);3.9199 (0.86); 3.6846 (0.33); 3.6661 (0.36); 3.6171 (0.37); 3.5995(0.37); 3.5078 (0.35); 3.3637 (1.04); 3.3424 (804.32); 3.3186 (9.85);3.2893 (0.5); 3.2722 (0.6); 3.2519 (0.38); 3.2175 (0.32); 3.0961 (0.41);3.0623 (0.35); 2.9842 (0.35); 2.8907 (1.32); 2.83 (0.8); 2.8117 (0.8);2.7313 (0.96); 2.6766 (1.05); 2.6721 (1.47); 2.6675 (1.09); 2.5424(0.67); 2.5255 (2.36); 2.5208 (3.63); 2.512 (75.12); 2.5075 (162.37);2.503 (218.4); 2.4984 (156.12); 2.494 (73.27); 2.3388 (0.55); 2.3342(1.08); 2.3297 (1.5); 2.3252 (1.13); 1.99 (16); 1.7116 (3.31); 1.6105(0.4); 1.5971 (0.55); 1.5894 (0.58); 1.576 (0.43); 1.4981 (0.96); 1.458(1.92); 1.44 (3.22); 1.4221 (1.86); 1.4094 (0.97); 1.3406 (3.68); 1.3235(3.33); 1.3135 (3.04); 1.2956 (3.01); 1.2777 (2.74); 1.2582 (2.19);1.2343 (5.2); 1.2036 (1.29); 1.1922 (5.62); 1.1863 (2.32); 1.1744(10.68); 1.1676 (3.46); 1.1566 (7.96); 1.1448 (5.05); 1.1332 (3.63);1.1153 (1.98); 1.0491 (1.91); 0.9496 (1.15); 0.9317 (1.85); 0.914(0.87); 0.8933 (0.63); 0.8748 (1.42); 0.8624 (1.03); 0.8539 (1.15);0.8363 (0.42); 0.1459 (0.45); 0.008 (3.24); −0.0002 (113.96); −0.0085(3.81); −0.1496 (0.43) Ex. 53, solvent: [DMSO], spectrometer: 399.95 MHz11.4811 (0.46); 9.5802 (3.86); 9.504 (0.61); 7.8067 (0.33); 7.7817(3.36); 7.7747 (1.02); 7.7681 (1.19); 7.7604 (4.49); 7.7135 (0.41);7.6917 (0.47); 7.6851 (0.47); 7.5943 (0.9); 7.5726 (1.01); 7.3651(0.37); 4.106 (0.36); 4.0549 (0.76); 4.037 (2.46); 4.0205 (16); 4.0015(0.98); 3.4808 (0.47); 3.4264 (0.76); 3.4141 (1.01); 3.366 (481.46);3.3609 (380.93); 3.3594 (381.76); 3.3541 (595.63); 3.3505 (698.07);3.0316 (0.61); 2.6772 (1.33); 2.6727 (1.85); 2.6681 (1.36); 2.5429(0.97); 2.5261 (3.27); 2.5213 (4.97); 2.5126 (89.86); 2.5081 (194.5);2.5036 (263.53); 2.4991 (189.65); 2.4946 (89.56); 2.4051 (1.69); 2.335(1.23); 2.3303 (1.72); 2.3258 (1.27); 2.0763 (1.33); 2.0394 (9.05);1.9899 (10.76); 1.9092 (0.76); 1.6335 (1.56); 1.6194 (3.67); 1.6124(4.01); 1.5991 (1.94); 1.5757 (0.35); 1.3543 (0.43); 1.2973 (1.85);1.2837 (3.68); 1.277 (4.01); 1.2623 (1.85); 1.2521 (0.95); 1.2369(1.14); 1.1922 (2.96); 1.1744 (5.8); 1.1566 (2.83); 0.008 (0.76);−0.0002 (21.52); −0.0085 (0.61) Ex. 54, solvent: [DMSO], spectrometer:399.95 MHz 9.4882 (0.79); 9.3813 (4.43); 8.5176 (2.05); 8.5137 (2.27);8.5056 (2.27); 8.5017 (2.28); 8.4323 (3.23); 8.4273 (3.41); 8.2561(0.5); 8.2509 (0.53); 7.952 (0.59); 7.7143 (0.68); 7.7082 (0.72); 7.6847(1.07); 7.6801 (1.7); 7.6753 (1.15); 7.6651 (1.28); 7.6603 (1.95);7.6556 (1.27); 7.5766 (0.52); 7.555 (0.77); 7.5036 (2.71); 7.4973(2.86); 7.4812 (0.43); 7.4689 (0.59); 7.4626 (0.76); 7.4508 (4.33);7.4415 (0.51); 7.4293 (4.72); 7.4088 (1.88); 7.3969 (1.79); 7.3893(1.66); 7.3773 (1.57); 6.9932 (1.56); 6.9868 (1.58); 6.9719 (1.46);6.9654 (1.45); 5.4683 (2.14); 5.4307 (2.45); 5.0433 (0.53); 4.9943(0.63); 4.9816 (2.41); 4.9544 (0.36); 4.9441 (2.09); 4.0808 (2.62);4.0555 (0.62); 4.0377 (1.82); 4.02 (1.85); 4.0022 (0.63); 3.9068 (16);3.3269 (326.92); 3.322 (337.09); 2.8902 (5.17); 2.7304 (4.11); 2.6791(0.48); 2.675 (1.04); 2.6704 (1.48); 2.6658 (1.11); 2.6613 (0.56);2.5408 (0.86); 2.5237 (2.77); 2.5102 (73.18); 2.5058 (152.67); 2.5013(207.94); 2.4967 (155.09); 2.4923 (79.01); 2.337 (0.46); 2.3326 (1.01);2.3281 (1.42); 2.3235 (1.05); 2.3191 (0.53); 2.0737 (0.39); 1.9884(7.83); 1.6127 (2.1); 1.5986 (4.95); 1.5917 (5.39); 1.5785 (2.38);1.2787 (0.41); 1.2653 (0.83); 1.2583 (1.18); 1.2433 (0.76); 1.2353(1.12); 1.2176 (1.97); 1.204 (4.14); 1.1973 (4.51); 1.1924 (3.36); 1.183(1.78); 1.1745 (4.42); 1.1567 (2.17); 0.008 (1.38); −0.0002 (45.87);−0.0084 (2.11) Ex. 55, solvent: [DMSO], spectrometer: 399.95 MHz 9.4969(1.3); 9.3847 (4.47); 7.9522 (0.67); 7.6698 (0.96); 7.664 (1.17); 7.6364(0.52); 7.615 (1.61); 7.6008 (1.05); 7.5951 (0.94); 7.5792 (0.35);7.5731 (0.36); 7.507 (3.9); 7.4855 (4.65); 7.4513 (3.32); 7.4447 (3.77);7.2367 (2.05); 7.2301 (2.11); 7.2153 (1.83); 7.2086 (1.89); 4.9577(1.05); 4.9518 (1.43); 4.9482 (1.23); 4.8765 (3.22); 4.7971 (5.72);4.7583 (2.3); 4.7061 (0.96); 4.3904 (2.06); 4.3516 (1.9); 4.3323 (0.37);4.2925 (0.75); 4.2475 (0.75); 4.2081 (0.32); 4.0563 (5.38); 4.0379(2.52); 4.0201 (2.62); 4.0023 (0.85); 3.9551 (0.69); 3.8648 (16); 3.6011(0.36); 3.5766 (15.78); 3.3572 (0.33); 3.3255 (554.45); 2.8905 (5.77);2.731 (4.53); 2.6751 (0.77); 2.6707 (1.1); 2.666 (0.83); 2.5407 (0.36);2.524 (1.72); 2.5105 (54.47); 2.5061 (115.62); 2.5015 (158.95); 2.497(121.97); 2.4927 (65.07); 2.3327 (0.86); 2.3283 (1.14); 2.3238 (0.89);2.1326 (0.37); 2.1203 (5.45); 1.9886 (10.49); 1.7799 (6.3); 1.7121(13.9); 1.6499 (0.4); 1.6077 (2.28); 1.5936 (5.52); 1.5872 (5.41);1.5736 (3.14); 1.5679 (4.32); 1.2928 (0.62); 1.2791 (1.24); 1.2727(1.44); 1.2583 (0.93); 1.2352 (1.63); 1.2184 (1.97); 1.205 (4.02);1.1984 (4.28); 1.1924 (4); 1.1846 (1.85); 1.1745 (5.9); 1.1568 (3.09);1.1023 (0.52); 1.0152 (11.7); 0.9974 (0.34); −0.0002 (0.61) Ex. 56,solvent: [DMSO], spectrometer: 601.6 MHz 9.4759 (0.64); 9.3699 (3.96);8.5556 (5.83); 8.5529 (3.5); 8.5482 (3.58); 8.5456 (6.22); 8.4651(0.81); 8.4626 (0.53); 8.4577 (0.53); 8.4551 (0.83); 7.9522 (0.41);7.7446 (0.57); 7.5812 (1.4); 7.5194 (2.55); 7.5151 (2.6); 7.4619 (4.25);7.4476 (4.7); 7.2711 (4.79); 7.2612 (4.76); 7.1362 (0.73); 7.1264(0.73); 7.1037 (1.56); 7.0993 (1.54); 7.0894 (1.48); 7.0849 (1.45);5.4328 (2.05); 5.4068 (2.29); 5.0763 (0.44); 5.0253 (2.42); 4.9994(2.01); 4.0725 (2.43); 4.0467 (1.03); 4.0348 (2.93); 4.023 (2.97);4.0112 (0.99); 3.9285 (16); 3.3673 (0.36); 3.3234 (775.68); 3.2995(6.23); 2.8904 (3.65); 2.7311 (2.88); 2.6191 (0.72); 2.6161 (1.53);2.6131 (2.16); 2.61 (1.53); 2.607 (0.72); 2.5406 (0.65); 2.5377 (0.44);2.5223 (5.37); 2.5193 (6.39); 2.5162 (5.82); 2.5074 (108.34); 2.5044(234.17); 2.5013 (320.07); 2.4983 (230.08); 2.4953 (105.4); 2.3916(0.64); 2.3885 (1.45); 2.3855 (2.03); 2.3824 (1.42); 2.3794 (0.63);2.0737 (0.79); 1.9885 (12.97); 1.604 (2.16); 1.5948 (4.81); 1.5903(5.36); 1.5814 (2.18); 1.2674 (0.33); 1.2583 (0.74); 1.2538 (0.79);1.2441 (0.52); 1.2351 (0.55); 1.2076 (1.71); 1.1984 (3.86); 1.1941(4.14); 1.1863 (4.31); 1.1745 (7.06); 1.1626 (3.5); 0.0965 (0.4); 0.0052(3.02); −0.0002 (99.19); −0.0058 (2.91); −0.1001 (0.39) Ex. 57, solvent:[DMSO], spectrometer: 399.95 MHz 11.5339 (4.33); 9.4933 (1.31); 9.4791(5.1); 7.7783 (0.46); 7.7659 (1.88); 7.7568 (1.13); 7.7496 (4.1); 7.7332(1.88); 7.697 (8.58); 7.6917 (3.71); 7.6793 (3.75); 7.6736 (2.13);7.6497 (0.47); 7.6332 (0.74); 7.6173 (0.48); 7.5851 (3.7); 7.567 (1.83);7.5617 (2.51); 7.5506 (0.43); 7.5346 (0.34); 7.5192 (0.33); 5.9815(0.48); 5.9665 (0.79); 5.95 (0.57); 5.9152 (0.52); 5.8999 (0.51); 5.8617(1.01); 5.8285 (6.59); 5.8124 (6.52); 5.3477 (1.24); 5.3423 (1.27);4.0562 (1.36); 4.0382 (3.76); 4.0202 (3.91); 4.0025 (1.35); 3.9786(1.07); 3.6883 (0.81); 3.5728 (0.36); 3.5567 (0.37); 3.5234 (0.37);3.5028 (0.42); 3.4858 (0.46); 3.4778 (0.41); 3.4639 (0.45); 3.4477(0.59); 3.4164 (0.76); 3.3245 (1168.23); 3.2622 (0.43); 3.2123 (0.32);3.1803 (0.58); 3.1683 (0.47); 3.0473 (1.21); 2.9933 (4.69); 2.9063(0.59); 2.8597 (1.25); 2.8422 (4.92); 2.6749 (3.65); 2.6707 (4.76);2.6666 (3.51); 2.5505 (1.32); 2.5403 (2.36); 2.5237 (16.88); 2.506(550.85); 2.5017 (693.41); 2.4974 (500.71); 2.438 (0.61); 2.4143 (0.41);2.393 (0.38); 2.3369 (10); 2.3286 (4.78); 2.3239 (3.48); 2.2986 (0.44);2.2881 (0.35); 2.2187 (0.35); 2.1917 (0.47); 2.074 (0.97); 2.0503(0.97); 1.9889 (16); 1.6079 (2.47); 1.5934 (6.31); 1.5869 (6.86); 1.5737(3.53); 1.5483 (0.66); 1.5334 (0.56); 1.3133 (0.48); 1.2989 (0.51);1.2759 (2.83); 1.2618 (6.03); 1.2551 (6.78); 1.2402 (4.56); 1.1923(4.5); 1.1745 (8.44); 1.1571 (4.12); 0.8537 (0.55); 0.0077 (1.92);0.0004 (50.97); −0.0002 (51.39); −0.0076 (2.47) Ex. 58, solvent: [DMSO],spectrometer: 399.95 MHz 11.4625 (0.76); 9.4924 (0.91); 7.7342 (0.69);7.7279 (0.87); 7.6972 (0.38); 7.6754 (0.52); 7.669 (0.44); 7.5846(0.89); 7.5628 (0.61); 5.2886 (0.42); 5.2653 (0.38); 5.2629 (0.4);5.2177 (0.4); 5.2149 (0.4); 5.1751 (0.34); 5.1722 (0.34); 5.0002 (0.7);4.9854 (0.68); 4.0553 (1.25); 4.0375 (3.8); 4.0197 (3.84); 4.0019(1.29); 3.3327 (56.56); 2.5244 (0.53); 2.5107 (9.02); 2.5065 (18.16);2.502 (23.94); 2.4976 (17.52); 2.4933 (8.69); 1.9892 (16); 1.6078(0.32); 1.5935 (0.8); 1.5866 (0.87); 1.5734 (0.37); 1.2731 (0.38);1.2595 (0.79); 1.2527 (0.87); 1.2381 (0.4); 1.1924 (4.32); 1.1746(8.51); 1.1568 (4.22) Ex. 59, solvent: [DMSO], spectrometer: 399.95 MHz11.651 (3.43); 9.5701 (3.87); 7.8258 (0.42); 7.8066 (0.45); 7.7856(1.77); 7.7798 (1.75); 7.7597 (1.67); 7.7539 (1.75); 7.4937 (2.27);7.4912 (2.53); 7.4879 (2.46); 4.055 (1.17); 4.0364 (16); 4.0195 (2.96);4.0017 (0.96); 3.3272 (189.39); 3.3038 (1.7); 2.6753 (2.02); 2.6707(2.77); 2.6662 (2.03); 2.6617 (1); 2.5409 (1.96); 2.538 (2); 2.5241(10.07); 2.5194 (14.6); 2.5106 (143.21); 2.5062 (290.59); 2.5017(381.24); 2.4971 (273.16); 2.4927 (130.54); 2.3372 (0.88); 2.3329(1.89); 2.3284 (2.64); 2.3238 (1.92); 1.9891 (12.1); 1.6247 (1.42);1.6106 (3.42); 1.6037 (3.59); 1.5904 (1.59); 1.3354 (0.45); 1.2977(0.37); 1.2887 (1.71); 1.2751 (3.39); 1.2684 (3.63); 1.254 (1.5); 1.2493(0.86); 1.2349 (1.15); 1.1921 (3.43); 1.1743 (6.77); 1.1565 (3.32);0.146 (0.95); 0.008 (8.15); −0.0002 (242.95); −0.0085 (7.93); −0.1497(0.99) Ex. 60, solvent: [DMSO], spectrometer: 399.95 MHz 7.794 (4.24);7.7727 (4.24); 7.6351 (0.76); 4.0377 (0.78); 4.0274 (0.64); 4.0196(1.38); 4.0064 (16); 3.3192 (128.67); 3.2968 (0.7); 2.8209 (1.39);2.8055 (1.44); 2.6747 (0.95); 2.6701 (1.33); 2.6657 (0.98); 2.5404(0.79); 2.5235 (3.49); 2.51 (67.6); 2.5057 (137.84); 2.5011 (183.23);2.4966 (131.99); 2.4922 (63.54); 2.4323 (0.41); 2.414 (0.36); 2.3324(1.13); 2.3278 (1.54); 2.3234 (1.25); 2.3189 (0.84); 2.2912 (1.59);2.2752 (1.59); 1.9886 (2.92); 1.8835 (2.17); 1.6149 (0.87); 1.4668(0.4); 1.449 (0.35); 1.3351 (0.44); 1.2492 (0.66); 1.2339 (0.36); 1.1922(0.88); 1.1744 (1.71); 1.1566 (0.85); 1.1112 (0.34); 1.0892 (0.48);1.084 (0.4); 1.0655 (0.87); 1.0372 (4.91); 1.0194 (10.33); 1.0015(4.75); 0.9043 (4.3); 0.8866 (9.1); 0.8688 (4.15); 0.008 (1.09); −0.0002(32.33); −0.0085 (1.18) Ex. 61, solvent: [DMSO], spectrometer: 399.95MHz 11.5111 (0.37); 11.475 (1.82); 7.8171 (0.36); 7.761 (1.76); 7.7563(1.78); 7.6607 (0.63); 7.6561 (0.62); 7.6393 (1.64); 7.6344 (1.68);7.6196 (2.16); 7.5979 (0.65); 4.0388 (7.82); 4.0199 (1.67); 3.3272(155.76); 3.3046 (0.44); 3.2089 (0.61); 3.0604 (0.48); 2.8649 (0.47);2.6801 (0.39); 2.6754 (0.85); 2.6708 (1.18); 2.6662 (0.84); 2.6616(0.37); 2.541 (0.64); 2.5242 (3.65); 2.5194 (6.12); 2.5108 (63.64);2.5063 (126.44); 2.5017 (165.51); 2.4971 (117.67); 2.4926 (54.8); 2.3375(0.45); 2.333 (0.89); 2.3285 (1.2); 2.3239 (0.84); 2.3193 (0.4); 1.9892(1.79); 1.717 (1.85); 1.4686 (0.61); 1.3975 (16); 1.3356 (0.56); 1.3185(0.45); 1.3025 (0.73); 1.2491 (0.7); 1.2357 (0.51); 1.2144 (1.84);1.1967 (3.53); 1.179 (1.74); 1.1744 (1.8); 1.1565 (0.59); 0.008 (0.73);−0.0002 (19.27); −0.0085 (0.58) Ex. 62, solvent: [DMSO], spectrometer:399.95 MHz 11.4809 (1.28); 7.7806 (1.15); 7.7762 (1.17); 7.6487 (0.33);7.6426 (0.35); 7.6268 (1.18); 7.6215 (1.31); 7.6147 (1.72); 7.593(0.33); 4.0556 (0.42); 4.0348 (5.9); 4.0202 (1.98); 4.0022 (0.4); 3.3283(21.01); 3.1067 (0.99); 2.8649 (5.51); 2.5245 (0.58); 2.511 (9.79);2.5067 (19.73); 2.5022 (26.27); 2.4977 (19.46); 2.4934 (9.59); 1.9895(4.55); 1.6728 (1.36); 1.4933 (1.02); 1.3975 (16); 1.1926 (1.27); 1.1748(2.51); 1.157 (1.23); −0.0002 (2.53) Ex. 63, solvent: [DMSO],spectrometer: 399.95 MHz 9.6002 (1.23); 7.7269 (1.04); 7.7055 (1.24);7.6766 (0.93); 7.6704 (0.97); 7.4809 (0.56); 7.4747 (0.53); 7.4597(0.48); 7.4533 (0.47); 4.8951 (0.42); 4.8795 (0.59); 4.864 (0.43);4.0855 (4.08); 4.0568 (1.41); 4.039 (4.12); 4.0212 (4.16); 4.0034(1.43); 3.3262 (2.69); 2.5117 (1.75); 2.5073 (3.52); 2.5028 (4.67);2.4983 (3.47); 2.4939 (1.71); 1.9898 (16); 1.617 (0.42); 1.6028 (1.05);1.596 (1.11); 1.5828 (0.47); 1.2947 (0.5); 1.281 (1.05); 1.2745 (1.1);1.2599 (0.4); 1.1934 (5.01); 1.1756 (9.46); 1.1578 (4.87); 1.0379(1.17); 1.0225 (1.27); 0.994 (1.27); 0.9787 (1.15); −0.0002 (1.31) Ex.64, solvent: [DMSO], spectrometer: 399.95 MHz 11.531 (5.19); 9.4981(6.09); 8.3176 (0.59); 7.7614 (4.9); 7.7551 (5.67); 7.69 (2.44); 7.6836(2.05); 7.6681 (3.54); 7.6617 (3.29); 7.588 (6.35); 7.5661 (4.3); 5.5721(1.17); 5.5509 (3.42); 5.5291 (3.53); 5.5072 (1.24); 4.0553 (0.61);4.0375 (1.86); 4.0197 (1.88); 4.0019 (0.63); 3.3757 (6.9); 2.6756 (1.2);2.671 (1.66); 2.6665 (1.24); 2.5379 (1.15); 2.5242 (6.33); 2.5193(9.89); 2.5108 (89.72); 2.5065 (179.68); 2.5019 (237.24); 2.4974(175.66); 2.4931 (88.49); 2.3331 (1.22); 2.3287 (1.67); 2.3242 (1.26);1.989 (7.98); 1.609 (2.14); 1.5947 (5.27); 1.5878 (5.67); 1.5746 (2.44);1.3977 (16); 1.3122 (0.32); 1.2725 (2.58); 1.2588 (5.23); 1.2521 (5.65);1.2375 (2.18); 1.1926 (2.19); 1.1748 (4.28); 1.157 (2.11); 0.8854(0.38); 0.0079 (1.5); −0.0002 (40.02); −0.0083 (1.91)

The intensity of sharp signals correlates with the height of the signalsin a printed example of an NMR spectrum in cm and shows the true ratiosof the signal intensities. In the case of broad signals, several peaksor the middle of the signal and their relative intensities may be shownin comparison to the most intense signal in the spectrum.

The lists of the ¹H NMR peaks are similar to the conventional ¹H NMRprintouts and thus usually contain all peaks listed in conventional NMRinterpretations.

In addition, like conventional ¹H NMR printouts, they may show solventsignals, signals of stereoisomers of the target compounds, whichlikewise form part of the subject-matter of the invention, and/or peaksof impurities.

In the reporting of compound signals in the delta range of solventsand/or water, our lists of ¹H NMR peaks show the usual solvent peaks,for example peaks of DMSO in DMSO-d₆ and the peak of water, whichusually have a high intensity on average.

The peaks of stereoisomers of the target compounds and/or peaks ofimpurities usually have a lower intensity on average than the peaks ofthe target compounds (for example with a purity of >90%).

Such stereoisomers and/or impurities may be typical of the particularpreparation process. Their peaks can thus help to identify reproductionof our preparation process with reference to “by-product fingerprints”.

A person skilled in the art calculating the peaks of the targetcompounds by known methods (MestreC, ACD simulation, but also withempirically evaluated expected values) can, if required, isolate thepeaks of the target compounds, optionally using additional intensityfilters. This isolation would be similar to the relevant peak picking inconventional ¹H NMR interpretation.

Preparation of the Starting Materials Ethyl3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate

10.16 g (254.2 mmol) of sodium hydride are suspended in 125 ml oftetrahydrofuran p.a. and cooled to −15° C. A solution of 15.0 g (127.1mmol) of 1-(1-chlorocyclopropyl)ethanone in 25 ml of tetrahydrofuranp.a. is added dropwise to this suspension. The suspension is stirred at−15° C. for 2 h, and 37.12 g (254.2 mmol) of diethyl oxalate are thenadded. After 3 h at room temperature, the reaction is quenched withice-water. The aqueous phase is extracted repeatedly with ethyl acetate.The combined organic phases are washed with saturated sodium chloridesolution, dried over sodium sulphate and filtered. The solvent isremoved on a rotary evaporator under reduced pressure.

The residue is dissolved in 150 ml of ethanol p.a. and boiled underreflux. 36.09 g (254.2 mmol) of methylhydrazine sulphate are added tothe mixture at reflux, and the mixture is boiled at reflux for a further4 h. After cooling, the reaction is concentrated under reduced pressureon a rotary evaporator, and the residue obtained in this manner is takenup in a mixture of water and ethyl acetate. The aqueous phase isextracted repeatedly with ethyl acetate. The combined organic phases arewashed with saturated sodium chloride solution, dried over sodiumsulphate and filtered. The solvent is removed on a rotary evaporatorunder reduced pressure. The crude product is purified by columnchromatography. This gives 4.34 g (15%) of ethyl3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate.

¹H-NMR (300 MHz, d₁-chloroform) δ=6.89 (s, 1H), 4.36 (q, 2H), 4.11 (s,3H), 1.35 (t, 3H) ppm;

Ethyl4-chloro-3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate

500 mg (2.19 mmol) of ethyl3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate are dissolvedin 10 ml of N,N-dimethylformamide p.a., and 438 mg (3.28 mmol)) ofN-chlorosuccinimide are added. The reaction mixture is heated at 80° C.for 15. The cooled reaction solution is diluted with water and extractedtwice with ethyl acetate. The combined organic phases are washed withsaturated sodium chloride solution, dried over sodium sulphate andfiltered. The solvent is removed under reduced pressure on a rotaryevaporator. The crude product is filtered through silica gel and elutedwith ethyl acetate. This gives 517 mg (80%) of ethyl4-chloro-3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate in apurity of 89%.

¹H-NMR (400 MHz, d₆-DMSO): δ=4.35 (q, 2H), 4.04 (s, 3H), 1.42-1.46 (m,2H), 1.31-1.38 (m, 5H) ppm.

HPLC-MS^(a)): log P=3.52, mass (m/z)=263 [M+H]⁺.

4-Chloro-3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylic acid

517 mg (1.76 mmol) of ethyl4-chloro-3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate(purity 89%) are dissolved in 10 ml of ethanol p.a. 3.5 ml (3.5 mmol) of1 N aqueous sodium hydroxide solution are then added to the solution,and the mixture is stirred at room temperature for 16 h. The reactionmixture is acidified by addition of 1 N hydrochloric acid. The aqueousphase is extracted twice with ethyl acetate. The combined organic phasesare washed with saturated sodium chloride solution, dried over sodiumsulphate and filtered. The solvent is removed under reduced pressure ona rotary evaporator. This gives 422 mg (99%) of4-chloro-3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylic acid.

¹H-NMR (400 MHz, d₆-DMSO): δ=4.02 (s, 3H), 1.31-1.42 (m, 4H) ppm.

HPLC-MS^(a)): log P=1.90, mass (m/z)=235 [M+H]⁺.

Ethyl 3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate

Ethyl 3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate isprepared from 1-(1-fluorocyclopropyl)ethanone analogously to the processdescribed in the synthesis of ethyl3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate.

¹H-NMR (300 MHz, d₆-chloroform) δ=6.90 (s, 1H), 4.34 (q, 2H), 4.13 (s,3H), 1.37 (t, 3H) ppm;

Ethyl4-chloro-3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylate

The preparation was carried out analogously to the preparation of ethyl4-chloro-3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylateusing ethyl 3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylateand 3 eq of N-chlorosuccinimide

¹H-NMR (400 MHz, d₆-DMSO): δ=4.36 (q, 2H), 4.06 (s. 3H), 1.38-1.44 (m,2H), 1.33 (t, 3H), 1.04-1.09 (m, 2H) ppm.

HPLC-MS^(a)): log P=3.07, mass (m/z)=247 [M+H]⁺.

4-Chloro-3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylic acid

The preparation was carried out analogously to the preparation of4-chloro-3-(1-chlorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylic acidusing ethyl 3-(1-fluorocyclopropyl)-1-methyl-1H-pyrazole-5-carboxylateand 5.0 eq of sodium hydroxide in methanol.

¹H-NMR (400 MHz, d₆-DMSO): δ=4.05 (s, 3H), 1.37-1.43 (m, 2H), 1.05-1.09(m, 2H) ppm.

HPLC-MS^(a)): log P=3.07, mass (m/z)=219 [M+H]⁺.

Methyl2-chloro-5-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzoate

4.0 g (12.8 mmol) of1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxylicacid are suspended in 50 ml of dichloromethane. 0.02 ml ofN,N-dimethylformamide and 3.54 ml (38.4 mmol) of oxalyl chloride arethen added in succession. The reaction mixture is then stirred first atroom temperature for 30 minutes and then under reflux for 30 minutes.The solvent is removed under reduced pressure on a rotary evaporator.The1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carbonylchloride formed is used for the subsequent synthesis step withoutfurther purification.

A solution of 4.24 g (12.8 mmol) of1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carbonylchloride in 25 ml of dichloromethane p.a. is added to a suspension of2.38 g (12.8 mmol) of methyl 5-amino-2-chlorobenzoate and 2.57 g (19.2mmol) of silver(I) cyanide in 50 ml of dichlormethane p.a., and themixture is stirred at room temperature for 16 h. The suspension is thenfiltered through silica gel and the product is eluted using a mixture ofcyclohexane and ethyl acetate (1:1). The organic phase is washedsuccessively three times with 6N hydrochloric acid and twice withsaturated sodium chloride solution. The organic phase is then dried oversodium sulphate, filtered and concentrated on a rotary evaporator underreduced pressure. This gives 5.75 g (93%) of methyl2-chloro-5-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzoate.

¹H-NMR (400 MHz, d₃-acetonitrile): δ=9.33 (s, 1H), 8.14 (d, 1H), 7.72(dd, 1H), 7.54 (d, 1H), 3.98 (s, 3H), 3.90 (s, 3H) ppm.

HPLC-MS^(a)): log P=4.05, mass (m/z)=480 [M+H]⁺.

2-Chloro-5-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzenecarboxylicacid

5.75 g (11.9 mmol) of methyl2-chloro-5-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzoateare dissolved in 30 ml of methanol p.A., and 15.0 ml (30.0 mmol) of 2 Naqueous sodium hydroxide solution are then added. The reaction mixtureis stirred at room temperature for 16 hours. The reaction solution isacidified carefully with 6 N hydrochloric acid, and the aqueous phase isthen extracted three times with ethyl acetate. The combined organicphases are washed once with saturated sodium chloride solution, driedover sodium sulphate and filtered. The solvent is removed under reducedpressure on a rotary evaporator. This gives 5.57 g of2-chloro-5-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzenecarboxylicacid as a colourless solid.

¹H-NMR (400 MHz, d₃-acetonitrile): δ=9.17 (s, 1H), 8.11 (d, 1H), 7.73(dd, 1H), 7.52 (d, 1H), 3.98 (s, 3H) ppm.

HPLC-MS^(a)): log P=3.18, mass (m/z)=466 [M+H]⁺.

Ethyl 3,4-bis(trifluoromethyl)-1H-pyrazole-5-carboxylate

Under protective gas, 7.57 g (63.0 mmol) of diazoethyl acetate areinitially charged in 200 ml of diethyl ether, and the temperature of themixture is adjusted to −70° C. 20.4 g (126 mmol) of hexafluorobutyne arethen introduced into the cooled solution. The reaction mixture is slowlywarmed to room temperature and stirred for 16 hours. The solvent is thenremoved on a rotary evaporator. This gives 17.0 g of ethyl3,4-bis(trifluoromethyl)-1H-pyrazole-5-carboxylate (98%) as a yellowoil.

¹H-NMR (400 MHz, d₃-acetonitrile): δ=4.42 (q, 2H), 1.38 (t, 3H) ppm.

GC-MS: retention time 3.48 min; mass (m/z)=276 [M]⁺.

1-Methyl-3,4-bis(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

3.0 g (10.9 mmol) of ethyl3,4-bis(trifluoromethyl)-1H-pyrazole-5-carboxylate and 4.5 g (32.6 mmol)of potassium carbonate are suspended in 70 ml of acetone, and 1.35 ml ofiodomethane (21.7 mmol) are added. The reaction mixture is stirred atroom temperature overnight. 54 ml (108 mmol) of 2 N aqueous sodiumhydroxide solution are added to the suspension. The solution is thenstirred at room temperature overnight. The reaction mixture is dilutedwith water, and most of the acetone is removed on a rotary evaporatorunder reduced pressure. The residue is adjusted to pH 2-3 using 1 Mhydrochloric acid. The aqueous reaction solution is extracted twice withethyl acetate. The combined organic phases are dried over magnesiumsulphate, filtered and concentrated under reduced pressure on a rotaryevaporator. This gives 2.7 g of1-methyl-3,4-bis(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (84%;purity 88%) as a brown solid.

¹H-NMR (400 MHz, d₃-acetonitrile): δ=4.12 (s, 3H) ppm.

HPLC-MS log P=1.47, mass (m/z)=263 [M+H]⁺.

Methyl 2-chloro-5-(methylamino)benzoate

55.0 g (296 mmol) of methyl 2-chloro-5-aminobenzoate and 49.1 g (356mmol) of potassium carbonate are suspended in 500 ml of acetonitrilep.a. 22.1 ml (356 mmol) of methyl iodide are added dropwise to thereaction mixture. The suspension is then boiled under reflux for 3hours. After cooling, the reaction mixture is filtered. The filtrate isdiluted with water. The aqueous phase is extracted twice with ethylacetate. The combined organic phases are dried over sodium sulphate andfiltered. The solvent is removed under reduced pressure on a rotaryevaporator. The crude product is purified by column chromatography. Thisgives 30.0 g (51%) of methyl 2-chloro-5-(methylamino)benzoate.

¹H-NMR (300 MHz, d₁-chloroform) δ=7.21 (d, 1H), 7.00 (d, 1H), 6.63 (d,1H), 3.90 (s, 3H), 2.86 (s, 3H) ppm.

5-Amino-2-chloro-N-(1-cyanocyclopropyl)benzamide

3.20 g (15.9 mmol) of 2-chloro-5-nitrobenzoic acid are initially chargedin 50 ml of dichloromethane p.a., and 0.06 ml of N,N-dimethylformamidep.a. is added. 2.08 ml (23.8 mmol) of oxalyl chloride are then added tothe reaction mixture. After 3 h at RT, the reaction mixture isconcentrated under reduced pressure on a rotary evaporator. The crudeproduct (2-chloro-5-nitrobenzoyl chloride) is reacted further withoutfurther purification.

2.36 g (19.8 mmol) of 1-aminocyclopropanecarbonitrile hydrochloride issuspended in 70 ml of chloroform p.a. With ice cooling, 6.93 ml (39.7mmol) of N-ethyldiisopropylamine are added to the suspension. A solutionof 3.50 g (15.9 mmol) of 2-chloro-5-nitrobenzoyl chloride in 5 ml ofchloroform p.a. is then added dropwise to the cooled mixture. Thereaction mixture is heated at 50° C. (oil bath temperature) for 4 h. Thereaction mixture is then stirred at room temperature for another 12 h.

The reaction mixture is concentrated under reduced pressure on a rotaryevaporator, and the residue is taken up in ethyl acetate. The organicphase is washed twice with 0.5 N hydrochloric acid, dried over sodiumsulphate and filtered. The solvent is removed under reduced pressure ona rotary evaporator. This gives 3.70 g (84%) of2-chloro-N-(1-cyanocyclopropyl)-5-nitrobenzamide.

¹H-NMR (400 MHz, d₆-DMSO): δ=9.59 (s, 1H), 8.36 (d, 1H), 8.31 (dd, 1H),7.85 (d, 1H), 1.55-1.61 (m, 2H), 1.32-1.37 (m, 2H) ppm.

HPLC-MS^(a)): log P=1.52, mass (m/z)=266 [M+H]⁺.

3.15 g of iron powder are suspended in 18 ml of 5% strength acetic acid,and a solution of 3.0 g of2-chloro-N-(1-cyanocyclopropyl)-5-nitrobenzamide in a mixture of 25 mlof ethyl acetate and 22.6 ml of glacial acetic acid is added. During theaddition, the internal temperature is kept below 45° C. The reactionmixture is stirred at room temperature for 14 hours and then filteredthrough Celite. The filtrate is diluted with water, and the aqueousphase is extracted three times with ethyl acetate. The combined organicphases are washed twice with a saturated sodium chloride solution, driedover magnesium sulphate, filtered and concentrated on a rotaryevaporator under reduced pressure. The crude product is triturated witha mixture of three parts of cyclohexane and one part of ethyl acetate,and the solid is filtered off. This gives 2.0 g (71%) of5-amino-2-chloro-N-(1-cyanocyclopropyl)benzamide.

¹H-NMR (400 MHz, d₆-DMSO): δ=9.20 (s, 1H), 7.07 (d, 1H), 6.62 (dd, 1H),6.57 (d, 1H), 1.51-1.57 (m, 2H), 1.17-1.24 (m, 2H) ppm.

HPLC-MS^(a)): log P=0.82, mass (m/z)=236 [M+H]⁺.

1-Methyl-4-(methylsulphanyl)-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylicacid

8.0 g (27.7 mmol) of1-methyl-4-nitro-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylic acid[preparation analogously to J. Med. Chem. 1987, 30, 91-96] are dissolvedin 100 ml of dichloromethane. 50 μl of N,N-dimethylformamide and 10.5 g(83.0 mmol) of oxalyl chloride are added successively to the solution.After 0.5 h at room temperature, the reaction is heated under reflux for0.5 h. The reaction mixture is cooled to room temperature. The solventsand excess oxalyl chloride are removed on a rotary evaporator underreduced pressure. The residue is dissolved in chloroform p.a. and slowlyadded dropwise to a suspension of 5.56 g (41.5 mmol) of silver(I)cyanide, 100 ml of chloroform p.a. and 56 ml of methanol p.a. Themixture is heated under reflux for 8 h and then cooled to roomtemperature. The reaction mixture is filtered through a short silica gelcolumn, and the column is rinsed with dichloromethane. The solvents areremoved on a rotary evaporator under reduced pressure.

This gives 8.5 g of methyl1-methyl-4-nitro-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylate. Thecrude product is used for the next reaction without furtherpurification.

¹H-NMR (600 MHz, d₆-DMSO): δ=4.16 (s, 3H), 3.93 (s, 3H) ppm.

HPLC-MS^(a)): log P=3.18, mass (m/z)=304 [M+H]⁺.

8.5 g (28.0 mmol) of methyl1-methyl-4-nitro-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylate and 850mg of palladium on carbon (10% palladium) are suspended in 100 ml ofmethanol. The autoclave is inertized with nitrogen and the reactionmixture is then stirred under a hydrogen atmosphere of 5 bar. After 22 hat RT, the mixture is filtered through Celite and the solvent is removedunder reduced pressure on a rotary evaporator. The crude product istaken up in dichloromethane and filtered through sodium sulphate. Thedichloromethane is then removed under reduced pressure on a rotaryevaporator.

This gives 6.7 g (86%) of methyl4-amino-1-methyl-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylate.

¹H-NMR (600 MHz, d₆-DMSO): δ=5.32 (s, 2H), 4.07 (s, 3H), 3.86 (s, 3H)ppm.

HPLC-MS^(a)): log P=2.52, mass (m/z)=274 [M+H]⁺.

2.0 g (7.32 mmol) of methyl4-amino-1-methyl-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylate and 1.38g (14.6 mmol) dimethyl disulphide are dissolved in 14 ml of acetonitrilep.a. A solution of 1.26 g (11.0 mmol) of tert-butyl nitrite in 5 ml ofacetonitrile p.a. is slowly added dropwise to this mixture. After theaddition has ended, the reaction mixture is stirred at room temperaturefor another 1 h. The reaction mixture is then poured into 1 Nhydrochloric acid. The aqueous phase is extracted three times with ethylacetate. The combined organic phases are washed twice with saturatedsodium chloride solution, dried over magnesium sulphate and filtered.The solvents are removed on a rotary evaporator under reduced pressure.

This gives 2.0 g (72%) of methyl1-methyl-4-(methylsulphanyl)-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylateas a 8:2 mixture of the desired product and the by-product methyl1-methyl-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylate.

¹H-NMR (400 MHz, d₆-DMSO): δ=4.12 (s, 3H), 3.94 (s, 3H), 2.34 (s, 3H)ppm.

HPLC-MS^(a)): log P=3.51, mass (m/z)=305 [M+H]⁺.

3.0 g of methyl1-methyl-4-(methylsulphanyl)-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylateare dissolved in 16 ml of methanol p.a. 16.5 ml of 2 N aqueous sodiumhydroxide solution are then added to the solution, and the mixture isstirred at room temperature for 16 h. The reaction mixture is dilutedwith ethyl acetate and then washed with 100 ml of 1 N hydrochloric acid.The acidic aqueous phase is extracted twice with ethyl acetate. Thecombined organic phases are washed with saturated sodium chloridesolution, dried over sodium sulphate and filtered. The solvents areremoved on a rotary evaporator under reduced pressure.

This gives 2.5 g (90%) of1-methyl-4-(methylsulphanyl)-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylicacid as an about 8:2 mixture of the desired product and the by-product1-methyl-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylic acid.

¹H-NMR (400 MHz, d₆-DMSO): δ=4.12 (s, 3H), 3.94 (s, 3H), 2.34 (s, 3H)ppm.

HPLC-MS log P=3.51, mass (m/z)=305 [M+H]⁺.

BIOLOGICAL EXAMPLES A. Activity of the Compounds Phaedon Test (PHAECOSpray Treatment) Solvents:

-   -   78.0 parts by weight of acetone    -   1.5 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration. Discs of Chinese cabbage leaves(Brassica pekinensis) are sprayed with an active compound preparation ofthe desired concentration and, after drying, populated with larvae ofthe mustard beetle (Phaedon cochleariae).

After a time of 7 days, the efficacy in % is determined. 100% means thatall of the beetle larvae have been killed; 0% means that none of thebeetle larvae have been killed.

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 100% at an application rate of 500 g/ha: 1,2, 3, 4, 5, 6, 7, 8, 9, 10

Spodoptera frugiperda Test (SPODFR Spray Treatment)

Solvents:

-   -   78.0 parts by weight of acetone    -   1.5 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration. Leaf discs of maize (Zea mays) aresprayed with an active compound formulation of the desired concentrationand, after drying, populated with caterpillars of the armyworm(Spodoptera frugiperda).

After 7 days, the efficacy in % is determined. 100% means that all ofthe caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

In this test, for example, the following compound of the PreparationExamples shows an efficacy of 83% at an application rate of 500 g/ha: 7

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 100% at an application rate of 500 g/ha: 2,4, 5, 6, 8, 9, 10

Myzus test (Myzupe spray treatment)

Solvents:

-   -   78 parts by weight of acetone    -   1.5 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration. Discs of Chinese cabbage leaves(Brassica pekinensis) infested by all stages of the green peach aphid(Myzus persicae) are sprayed with an active compound preparation of thedesired concentration.

After 6 days, the efficacy in % is determined. 100% means that all ofthe aphids have been killed; 0% means that none of the aphids have beenkilled.

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 90% at an application rate of 500 g/ha: 5,9

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 100% at an application rate of 500 g/ha: 2,4, 6, 8, 10

Tetranychus Test, OP-Resistant (TETRUR Spray Treatment) Solvents:

-   -   78.0 parts by weight of acetone    -   1.5 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration. Discs of bean leaves (Phaseolusvulgaris) which are infested by all stages of the greenhouse red spidermite (Tetranychus urticae) are sprayed with an active compoundpreparation of the desired concentration.

After a time of 6 days, the efficacy in % is determined. 100% means thatall of the spider mites have been killed; 0% means that none of thespider mites have been killed.

In this test, for example, the following compound of the PreparationExamples shows an efficacy of 90% at an application rate of 500 g/ha: 10

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 100% at an application rate of 500 g/ha: 1,2, 3, 4, 5, 6, 7, 8, 9.

Ctenocephalides felis Oral (CTECFE)Solvent: 1 part by weight of dimethyl sulphoxide

For the purpose of producing a suitable preparation of active compound,10 mg of active compound are mixed with 0.5 ml of dimethyl sulphoxide. Aportion of the concentrate is diluted with citrated cattle blood, andthe desired concentration is prepared.

About 20 unfed adult fleas (Ctenocephalides felis) are placed into achamber which is closed at the top and bottom with gauze. A metalcylinder whose bottom end is closed with parafilm is placed onto thechamber. The cylinder contains the blood/active compound preparation,which can be taken up by the fleas through the parafilm membrane. After2 days, the kill in % is determined. 100% means that all of the fleashave been killed; 0% means that none of the fleas have been killed.

In this test, for example, the following compound of the PreparationExamples shows, at an application rate of 100 ppm, an effect of 80%: 7

In this test, for example, the following compounds of the PreparationExamples show, at an application rate of 100 ppm, an effect of 100%: 2,6, 8, 9, 10

Lucilia cuprina Test (LUCICU)Solvent: dimethyl sulphoxide

To produce a suitable preparation of active compound, 10 mg of activecompound are mixed with 0.5 ml of dimethyl sulphoxide, and theconcentrate is diluted with water to the desired concentration. Vesselscontaining horse meat treated with the active compound preparation ofthe desired concentration are populated with about 20 Lucilia cuprinalarvae.

After 2 days, the kill in % is determined. 100% means that all larvaehave been killed; 0% means that no larvae have been killed.

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 100% at an application rate of 100 ppm: 6,7, 8, 9, 10

Musca domestica Test (MUSCDO)Solvent: dimethyl sulphoxide

To produce a suitable preparation of active compound, 10 mg of activecompound are mixed with 0.5 ml of dimethyl sulphoxide, and theconcentrate is diluted with water to the desired concentration. Vesselscontaining a sponge treated with the active compound preparation of thedesired concentration are populated with adult Musca domestica.

After 2 days, the kill in % is determined. 100% means that all of theflies have been killed; 0% means that none of the flies have beenkilled.

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 100% at an application rate of 100 ppm: 6,7, 8, 10

Boophilus microplus Test (BOOPMI Injection)Solvent: dimethyl sulphoxide

To produce a suitable preparation of active compound, 10 mg of activecompound are mixed with 0.5 ml of solvent, and the concentrate isdiluted with solvent to the desired concentration. The active compoundsolution is injected into the abdomen (Boophilus microplus), and theanimals are transferred into dishes and stored in a climate-controlledroom. The activity is assessed by laying of fertile eggs.

After 7 days, the efficacy in % is determined 100% means that none ofthe ticks has laid any fertile eggs.

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 100% at an application rate of 20μg/animal: 2, 6, 7, 8, 9, 10

Boophilus microplus Test (DIP)

Test animals: adult engorged Boophilus microplus females of theSP-resistant Parkhurst strain

Solvent: dimethyl sulphoxide

10 mg of active compound are dissolved in 0.5 ml of dimethyl sulphoxide.For the purpose of preparing a suitable formulation, the active compoundsolution is diluted with water to the concentration desired in eachcase.

This active compound preparation is pipetted into tubes. 8-10 ticks aretransferred into a further tube with holes. The tube is immersed intothe active compound formulation, and all ticks are completely wetted.After the liquid has rum off, the ticks are transferred to filter discsin plastic dishes and kept in a climatized room. The activity isassessed after 7 days by laying of fertile eggs. Eggs whose fertility isnot outwardly visible are stored in glass tubes in a climate-controlledcabinet until the larvae hatch. An efficacy of 100% means that none ofthe ticks has laid any fertile eggs.

In this test, for example, the following compounds of the PreparationExamples show an efficacy of 100% at an application rate of 100 ppm: 6,8, 9, 10

Amblyomma hebaraeum Test (AMBYHE)Solvent: dimethyl sulphoxide

To produce a suitable preparation of active compound, 10 mg of activecompound are mixed with 0.5 ml of dimethyl sulphoxide, and theconcentrate is diluted with water to the desired concentration.

Tick nymphs (Amblyomma hebraeum) are placed into perforated plasticbeakers and immersed in the desired concentration for one minute. Theticks are transferred on filter paper into a Petri dish and stored in aclimate-controlled cabinet.

After 42 days, the kill in % is determined. 100% means that all of theticks have been killed; 0% means that none of the ticks have beenkilled.

In this test, for example, the following compound of the PreparationExamples shows, at an application rate of 100 ppm, an effect of 100%: 10

B. Biological Comparative Tests

Spodoptera frugiperda Test (SPODFR Spray Treatment)

Solvents:

-   -   78.0 parts by weight of acetone    -   1.5 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in g/ha).

Leaf discs of maize (Zea mays) are sprayed with an active compoundformulation of the desired concentration and, after drying, populatedwith caterpillars of the armyworm (Spodoptera frugiperda).

After the desired period of time, the effect in % is determined 100%means that all of the caterpillars have been killed; 0% means that noneof the caterpillars have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Myzus Test (MYZUPE Spray Treatment) Solvents:

-   -   78.0 parts by weight of acetone    -   1.5 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in g/ha).

Discs of Chinese cabbage leaves (Brassica pekinensis) infested by allstages of the green peach aphid (Myzus persicae) are sprayed with anactive compound preparation of the desired concentration.

After the desired period of time, the effect in % is determined 100%means that all of the aphids have been killed; 0% means that none of theaphids have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Phaedon Test (PHAECO Spray Treatment) Solvents:

-   -   78.0 parts by weight of acetone    -   1.5 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in g/ha).

Discs of Chinese cabbage leaves (Brassica pekinensis) are sprayed withan active compound preparation of the desired concentration and, afterdrying, populated with larvae of the mustard beetle (Phaedoncochleariae).

After the desired period of time, the effect in % is determined 100%means that all of the beetle larvae have been killed; 0% means that noneof the beetle larvae have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Tetranychus Test, OP-Resistant (TETRUR Spray Treatment) Solvents:

-   -   78.0 parts by weight of acetone    -   1.5 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in g/ha).

Discs of bean leaves (Phaseolus vulgaris) which are infested by allstages of the greenhouse red spider mite (Tetranychus urticae) aresprayed with an active compound preparation of the desiredconcentration.

After the desired period of time, the effect in % is determined 100%means that all of the spider mites have been killed; 0% means that noneof the spider mites have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Phaedon cochleariae Spray Test (PHAECO)Solvent: 7 parts by weight of dimethylformamideEmulsifier: 2 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in ppm). If the addition of ammoniumsalts or/and penetrants is required, these are in each case added in aconcentration of 1000 ppm to the solution of the preparation.

Cabbage leaves (Brassica oleracea) are sprayed with an active compoundpreparation of the desired concentration and populated with larvae ofthe mustard beetle (Phaedon cochleariae).

After the desired period of time, the kill in % is determined 100% meansthat all of the beetle larvae have been killed; 0% means that none ofthe beetle larvae have been killed.

In this test, for example, the following compound of the PreparationExamples shows superior efficacy to the prior art: see table

Plutella xylostella Spray Test (PLUTMA)Solvent: 7 parts by weight of dimethylformamideEmulsifier: 2 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in ppm). If the addition of ammoniumsalts or/and penetrants is required, these are in each case added in aconcentration of 1000 ppm to the solution of the preparation.

Cabbage leaves (Brassica oleracea) are sprayed with an active compoundpreparation of the desired concentration and infected with larvae of thediamondback moth (Plutella xylostella).

After the desired period of time, the kill in % is determined 100% meansthat all caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

In this test, for example, the following compound of the PreparationExamples shows superior efficacy to the prior art: see table

Spodoptera frugiperda Spray Test (SPODFR)Solvent: 7 parts by weight of dimethylformamideEmulsifier: 2 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in ppm). If the addition of ammoniumsalts or/and penetrants is required, these are in each case added in aconcentration of 1000 ppm to the solution of the preparation.

Cotton leaves (Gossypium hirsutum) are sprayed with an active compoundformulation of the desired concentration and populated with caterpillarsof the armyworm (Spodoptera frugiperda).

After the desired period of time, the kill in % is determined 100% meansthat all caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Heliothis armigera Spray Test (HELIAR)Solvent: 7 parts by weight of dimethylformamideEmulsifier: 2 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in ppm). If the addition of ammoniumsalts or/and penetrants is required, these are in each case added in aconcentration of 1000 ppm to the solution of the preparation.

Cotton plants (Gossypium hirsutum) are sprayed with an active compoundformulation of the desired concentration and, after drying, populatedwith caterpillars of the cotton bollworm (Heliothis armigera). After thedesired period of time, the kill in % is determined 100% means that allcaterpillars have been killed; 0% means that none of the caterpillarshave been killed.

In this test, for example, the following compound of the PreparationExamples shows superior efficacy to the prior art: see table

Tetranychus urticae Spray Test, OP-Resistant (TETRUR)Solvent: 7 parts by weight of dimethylformamideEmulsifier: 2 parts by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration (in ppm). If the addition of ammoniumsalts or/and penetrants is required, these are in each case added in aconcentration of 1000 ppm to the solution of the preparation.

Bean plants (Phaseolus vulgaris) which are heavily infested by allstages of the greenhouse red spider mite (Tetranychus urticae) aresprayed with an active compound preparation of the desiredconcentration.

After the desired period of time, the effect in % is determined 100%means that all of the spider mites have been killed; 0% means that noneof the spider mites have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Nilaparvata lugens Spray Test (NILALU)

Solvents:

-   -   52.5 parts by weight of acetone    -   7 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration. If the addition of ammonium saltsor/and penetrants is required, these are in each case added in aconcentration of 1000 ppm to the solution of the preparation.

Rice plants (Oryza sativa) are sprayed with an active compoundpreparation of the desired concentration and then populated with larvaeof the brown planthopper (Nilaparvata lugens).

After the desired period of time, the effect in % is determined 100%means that all of the planthoppers have been killed; 0% means that noneof the planthoppers have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Frankliniella occidentalis Spray Test (FRANOC)

Solvents:

-   -   52.5 parts by weight of acetone    -   7 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration. If the addition of ammonium saltsor/and penetrants is required, these are in each case added in aconcentration of 1000 ppm to the solution of the preparation. Discs ofleaves of common beans (Phaseolus vulgaris) are sprayed with an activecompound preparation of the desired concentration and then infected witha mixed thrips population (Frankliniella occidentalis).

After the desired period of time, the effect in % is determined 100%means that all thrips have been killed; 0% means that none of the thripshave been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Liriomyza trifolii Spray Test (LIRITR)

Solvents:

-   -   52.5 parts by weight of acetone    -   7 parts by weight of dimethylformamide        Emulsifier: 0.5 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvents andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration. If the addition of ammonium saltsor/and penetrants is required, these are in each case added in aconcentration of 1000 ppm to the solution of the preparation. Discs ofbean leaves (Phaseolus vulgaris) which are infested by larvae of theleaf-mining fly (Liriomyza trifolii) are sprayed with an active compoundpreparation of the desired concentration.

After the desired period of time, the effect in % is determined 100%means that all of the leaf-mining flies have been killed; 0% means thatnone of the leaf-mining flies have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Ctenocephalides felis Oral (CTECFE)Solvent: 1 part by weight of dimethyl sulphoxide

For the purpose of preparing an appropriate active compound formulation,10 mg of active compound are mixed with 0.5 ml of dimethyl sulphoxide. Aportion of the concentrate is diluted with citrated cattle blood, andthe desired concentration is prepared.

About 20 unfed adult fleas (Ctenocephalides felis) are placed into achamber which is closed at the top and bottom with gauze. A metalcylinder whose bottom end is closed with parafilm is placed onto thechamber. The cylinder contains the blood/active compound preparation,which can be taken up by the fleas through the parafilm membrane.

After the desired period of time, the kill in % is determined 100% meansthat all of the fleas have been killed; 0% means that none of the fleashave been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Musca domestica Test (MUSCDO)Solvent: dimethyl sulphoxide

To produce a suitable preparation of active compound, 10 mg of activecompound are mixed with 0.5 ml of dimethyl sulphoxide, and theconcentrate is diluted with water to the desired concentration.

Vessels containing a sponge treated with the active compound formulationof the desired concentration are populated with adult Musca domestica.

After the desired period of time, the kill in % is determined. 100%means that all of the flies have been killed; 0% means that none of theflies have been killed.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Boophilus microplus Test (DIP)Test animals: adult engorged Boophilus microplus females of theSP-resistant Parkhurst strainSolvent: dimethyl sulphoxide

10 mg of active compound are dissolved in 0.5 ml of dimethyl sulphoxide.For the purpose of preparing a suitable formulation, the active compoundsolution is diluted with water to the concentration desired in each case(in ppm).

This active compound preparation is pipetted into tubes. 8-10 ticks aretransferred into a further tube with holes. The tube is immersed intothe active compound formulation, and all ticks are completely wetted.After the liquid has run out, the ticks are transferred onto filterdiscs in plastic dishes and stored in a climate-controlled room.

The activity is assessed after the desired time by laying of fertileeggs. Eggs whose fertility is not evident from the outside are kept inglass tubes in a climate-controlled cabinet until the larvae havehatched. An effect of 100% means that none of the ticks has laid anyfertile eggs.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Boophilus microplus Test (BOOPMI Injection)Solvent: dimethyl sulphoxide

To produce a suitable preparation of active compound, 10 mg of activecompound are mixed with 0.5 ml of solvent, and the concentrate isdiluted with solvent to the desired concentration (in μg/animal).

The active compound solution is injected into the abdomen (Boophilusmicroplus), and the animals are transferred into dishes and stored in aclimate-controlled room.

After 7 days, the efficacy in % is determined. The activity is assessedby laying of fertile eggs. 100% means that none of the ticks has laidany fertile eggs.

In this test, for example, the following compounds of the PreparationExamples show superior efficacy to the prior art: see table

Animal Substance Structure species Concentration % Activity dat Ex. No.Ik-136 known from WO 2010/051926 A2

MYZUPE TETRUR PHAECO NILALU CTECFE BOOPMI  20 g/ha  20 g/ha  0.8 ppm  20g/ha  0.8 ppm  0.032 μg/animal  20 ppm  0 6dat  0 6dat  0 7dat  0 7dat 30 2dat  0 7dat  0 7dat Ex. No. 6 according to the invention

MYZUPE TETRUR PHAECO NILALU CTECFE BOOPMI  20 g/ha  20 g/ha  0.8 ppm  20g/ha  0.8 ppm  0.032 μg/animal  20 ppm  70 6dat 100 6dat 100 7dat  907dat  80 2dat  70 7dat 100 7dat Ex. No. Ik-132 known from WO 2010/051926A2

MYZUPE PHAECO PLUTMA SPODFR TETRUR CTECFE BOOPMI 100 g/ha  0.8 ppm  20ppm  20 ppm  4 ppm  0.8 ppm  0.032 μg/animal  20 ppm  0 6dat  5 7dat  57dat  50 7dat  30 7dat  30 2dat  0 7dat  30 7dat Ex. No. 8 according tothe invention

MYZUPE PHAECO PLUTMA SPODFR TETRUR CTECFE BOOPMI 100 g/ha  0.8 ppm  20ppm  20 ppm  4 ppm  0.8 ppm  0.032 μg/amimal  20 ppm 100 6dat 100 7dat100 7dat 100 7dat  95 7dat  90 2dat 100 7dat 100 7dat Ex. No. Ik-1 knownfrom WO 2010/051926 A2

SPODFR HELIAR TETRUR FRANOC NILALU CTECFE  20 ppm  20 ppm  4 ppm  20g/ha 500 g/ha  0.8 ppm  20 7dat  45 7dat  40 7dat  0 7dat  0 7dat  02dat Ex. No. Ik-296 known from WO 2010/051926 A2

MYZUPE FRANOC LIRITR NILALU 100 g/ha 500 g/ha 500 g/ha 500 g/ha  0 6dat 60 7dat  0 7dat  0 7dat Ex. No. Ik-47 known from WO 2010/051926 A2

MYZUPE PHAECO PLUTMA SPODFR HELIAR TETRUR FRANOC NILALU CTECFE MUSCDOBOOPMI 500 g/ha  20 g/ha  20 ppm  20 ppm  20 ppm  20 ppm 500 g/ha 500g/ha  20 ppm 100 ppm  0.8 μg/animal  0 6dat  0 7dat  0 7dat  0 7dat  07dat  30 7dat  0 7dat  0 7dat  50 2dat  0 2dat  50 7dat Ex. No. Ik-286known from WO 2010/051926 A2

MYZUPE PHAECO CTECFE BOOPMI  20 g/ha 100 g/ha  4 ppm 100 ppm  0.16μg/animal  0 6dat  0 7dat  0 2dat  40 7dat  20 7dat Ex. No. Ik-279 knownfrom WO 2010/051926 A2

MYZUPE PHAECO SPODFR TETRUR  20 g/ha  20 g/ha 100 g/ha  4 ppm  0 6dat  07dat  50 7dat  0 7dat Ex. No. Ik-280 known from WO 2010/051926 A2

PLUTMA PHAECO SPODFR HELIAR NILALU  20 ppm  4 ppm  20 ppm 100 ppm 100g/ha  65 7dat  0 7dat  40 7dat  0 7dat  0 7dat Ex. No. 10 according tothe invention

MYZUPE PHAECO SPODFR PLUTMA HELIAR TETRUR FRANOC LIRITR NILALU CTECFEMUSCDO BOOPMI 500 g/ha 100 g/ha  20 g/ha 100 g/ha  20 g/ha  4 ppm 100g/ha  20 ppm  20 ppm 100 ppm  20 ppm  20 ppm  4 ppm 500 g/ha  20 g/ha500 g/ha 500 g/ha 100 g/ha  20 ppm  4 ppm  0.8 ppm 100 ppm  0.8μg/animal  0.16 μg/animal 100 ppm 100 6dat 100 6dat  80 6dat 100 7dat100 7dat 100 7dat 100 7dat 100 7dat 100 7dat 100 7dat 100 7dat 100 7dat100 7dat 100 7dat  90 7dat 100 7dat 100 7dat 100 7dat 100 2dat  98 2dat 90 2dat 100 2dat 100 7dat  80 7dat 100 7dat Ex. No. Ik-175 known fromWO 2010/051926 A2

MYZUPE PHAECO NILALU 100 g/ha  4 ppm 500 g/ha  0 6dat  10 7dat  0 7datEx. No. 14 according to the invention

MYZUPE PHAECO NILALU 100 g/ha  4 ppm 500g/ha 100 6dat 100 7dat  80 4datEx. No. Ik-155 known from WO 2010/051926 A2

MYZUPE TETRUR 100 g/ha 100 g/ha  0 6dat  0 6dat Ex. No. 14 according tothe invention

MYZUPE TETRUR 100 g/ha 100 g/ha 100 6dat 100 6dat

1. A compound of formula (I)

in which R¹ represents hydrogen, optionally substituted C₁-C₆-alkyl,C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₇-cycloalkyl, C₁-C₆-alkylcarbonyl,C₁-C₆-alkoxycarbonyl, cyano-C₁-C₂-alkyl, aryl-(C₁-C₃)-alkyl,heteroaryl-(C₁-C₃)-alkyl, chemical grouping A₁ represents CR² ornitrogen, A₂ represents CR³ or nitrogen, A₃ represents CR⁴ or nitrogenand A₄ represents CR⁵ or nitrogen, but where not more than three ofchemical groupings A₁ to A₄ simultaneously represent nitrogen; R², R³,R⁴ and R⁵ independently of one another represent hydrogen, halogen, CN,NO₂, optionally substituted C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, C₁-C₆-alkylsulphinyl,C₁-C₆-haloalkylsulphinyl, C₁-C₆-alkylsulphonyl,C₁-C₆-haloalkylsulphonyl, C₁-C₆-alkylamino, N,N-di-C₁-C₆alkylamino,N—C₁-C₆-alkylaminocarbonyl, N—C₃-C₆-cycloalkylaminocarbonyl or(C₁-C₃-alkoxy)carbonyl; if none of groupings A₂ and A₃ representsnitrogen, R³ and R⁴ together with the carbon atom to which they areattached may form a 5- or 6-membered ring which contains 0, 1 or 2nitrogen atoms and/or 0 or 1 oxygen atom and/or 0 or 1 sulphur atom, orif none of groupings A₁ and A₂ represents nitrogen, R² and R³ togetherwith the carbon atom to which they are attached may form a 6-memberedring which contains 0, 1 or 2 nitrogen atoms; W represents oxygen orsulphur; R⁶ represents hydrogen, optionally substituted C₁-C₆-alkyl,aryl-(C₁-C₃)-alkyl, heteroaryl-(C₁-C₃)-alkyl, C₂-C₆-alkenyl,C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, (C₁-C₃-alkyl)-C₃-C₆-cycloalkyl and(C₃-C₆-cycloalkyl)-C₁-C₃-alkyl, C₁-C₆-alkylcarbonyl,C₁-C₆-alkoxycarbonyl; Q represents

E represents a bond, —CH₂—, S, SO, SO₂, —S—CH₂—, —SO—CH₂—, —SO₂—CH₂—,—CH₂—S—CH₂—, —CH₂—SO—CH₂—, —CH₂—SO₂—CH₂—, —S—CH₂—CH₂—, —SO—CH₂—CH₂—,—SO₂—CH₂—CH₂—, —NR⁶—CH₂—, —CH₂—NR⁶—CH₂—; R⁷ represents cyano orC(═S)NH₂; Z¹ represents optionally substituted C₁-C₆-haloalkyl orC₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, and Z² represents halogen,cyano, nitro or optionally substituted C₁-C₆-haloalkyl, C₁-C₆-alkylthio,C₁-C₆-haloalkylthio, C₁-C₆-alkylsulphinyl, C₁-C₆-haloalkylsulphinyl,C₁-C₆-alkylsulphonyl, C₁-C₆-haloalkylsulphonyl, and Z³ representshydrogen or optionally substituted C₁-C₆-alkyl, C₁-C₄-alkenyl,C₁-C₄-alkynyl, C₁-C₆-haloalkyl.
 2. A compound of formula (I) accordingto claim 1, in which R¹ represents hydrogen, methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, methoxymethyl,ethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl,n-propylcarbonyl, isopropylcarbonyl, s-butylcarbonyl, t-butylcarbonyl,methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl,s-butoxycarbonyl, t-butoxycarbonyl, cyanomethyl, 2-cyanoethyl, benzyl,4-methoxybenzyl, pyrid-2-ylmethyl, pyrid-3-ylmethyl, pyrid-4-ylmethyl,4-chloropyrid-3-ylmethyl; chemical grouping A₁ represents CR² ornitrogen, A₂ represents CR³ or nitrogen, A₃ represents CR⁴ or nitrogenand A₄ represents CR⁵ or nitrogen, but where not more than three ofchemical groupings A₁ to A₄ simultaneously represent nitrogen; R² and R⁵independently of one another represent hydrogen, methyl, fluorine orchlorine and R³ and R⁴ independently of one another represent hydrogen,fluorine, chlorine, bromine, CN, NO₂, methyl, ethyl, fluoromethyl,difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy,n-propoxy, 1-methylethoxy, fluoromethoxy, difluoromethoxy,chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy,2,2,2-trifluoroethoxy, 2-chloro-2,2-difluoroethoxy, pentafluoroethoxy,methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl,trifluoromethylsulphinyl; where W represents oxygen, R⁶ representshydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,s-butyl, t-butyl, methoxymethyl, ethoxymethyl, propoxymethyl,methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl,s-butylcarbonyl, t-butylcarbonyl, methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, isopropoxycarbonyl, s-butoxycarbonyl,t-butoxycarbonyl, cyanomethyl, 2-cyanoethyl, benzyl, 4-methoxybenzyl,pyrid-2-ylmethyl, pyrid-3-ylmethyl, pyrid-4-ylmethyl,4-chloropyrid-3-ylmethyl; Q represents

E represents a bond or —CH₂—; R⁷ represents cyano or C(═S)NH₂; Z¹represents difluoromethyl, trichloromethyl, chlorodifluoromethyl,dichlorofluoromethyl, trifluoromethyl, bromodichloromethyl,chloromethyl, bromomethyl, 1-fluoroethyl, 1-fluoro-1-methylethyl,2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,1,2,2,2-tetrafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethyl,2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl,pentafluoroethyl, pentafluoro-t-butyl, heptafluoro-n-propyl,heptafluoroisopropyl, nonafluoro-n-butyl, cyclopropyl,1-chlorocyclopropyl, 1-fluorocyclopropyl, 1-bromocyclopropyl,1-cyanocyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl or2,2-difluoro-1-methylcyclopropyl, and Z² represents halogen, cyano,nitro, difluoromethyl, trichloromethyl, chlorodifluoromethyl,dichlorofluoromethyl, trifluoromethyl, bromodichloromethyl,chloromethyl, bromomethyl, 1-fluoroethyl, 1-fluoro-1-methylethyl,2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,1,2,2,2-tetrafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethyl,2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, 1,1-difluoroethyl,pentafluoroethyl, pentafluoro-t-butyl, heptafluoro-n-propyl,heptafluoroisopropyl, nonafluoro-n-butyl, methylthio, methylsulphinyl,methylsulphonyl, ethylthio, ethylsulphinyl, ethylsulphonyl,trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl,and Z³ represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, s-butyl, t-butyl, ethenyl, 1-propenyl, 2-propenyl, ethynyl,1-propynyl, 1-butynyl, difluoromethyl, trichloromethyl,chlorodifluoromethyl, dichlorofluoromethyl, trifluoromethyl,chloromethyl, bromomethyl, 1-fluoroethyl, 1-fluoro-1-methylethyl,2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl.
 3. A compound offormula (I) according to claim 1, in which Z¹ representstrifluoromethyl, 1-chlorocyclopropyl, 1-fluorocyclopropyl orpentafluoroethyl, Z² represents trifluoromethyl, nitro, methylthio,methylsulphinyl, methylsulphonyl, fluorine, chlorine, bromine or iodine,Z³ represents methyl, ethyl, n-propyl or hydrogen, R¹ representshydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,s-butyl, t-butyl, methoxymethyl, ethoxymethyl, propoxymethyl,methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl,s-butylcarbonyl, t-butylcarbonyl, methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, isopropoxycarbonyl, s-butoxycarbonyl,t-butoxycarbonyl, cyanomethyl, 2-cyanoethyl, benzyl, 4-methoxybenzyl,pyrid-2-ylmethyl, pyrid-3-ylmethyl, pyrid-4-ylmethyl,4-chloropyrid-3-ylmethyl, A¹, A² and A⁴ represent CH, A₃ represents CR⁴and R⁴ represents fluorine, chlorine, bromine or iodine, R⁶ representshydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,s-butyl, t-butyl, W represents oxygen and Q represents1-cyanocyclopropyl.
 4. A compound of formula (I) according to claim 1,in which Z¹ represents trifluoromethyl, 1-chlorocyclopropyl,1-fluorocyclopropyl or pentafluoroethyl, Z² represents trifluoromethyl,chlorine or Z³ represents methyl, R¹ represents hydrogen, methyl, ethyl,A¹, A² and A⁴ represent CH, A₃ represents CR⁴ and R⁴ representschlorine, R⁶ represents hydrogen, methyl, ethyl, W represents oxygen andQ represents 1-cyanocyclopropyl.
 5. A compound of formula (I) accordingto claim 1, capable of being used for controlling an insect, an arachnidand/and a nematode.
 6. A pharmaceutical composition comprising at leastone compound according to claim
 1. 7. A compound according to claim 1capable of being used as a medicament.
 8. A compound of formula (I)according to claim 1, capable of being used for preparing apharmaceutical composition for controlling a parasite on an animal.
 9. Aprocess for preparing a crop protection composition comprising mixing acompound of formula (I) according to claim 1, and at least one customaryextender and/or surfactant.
 10. A method for controlling a pest,comprising allowing a compound of formula (I) according to claim 1, toact on a pest and/or a habitat thereof.
 11. A compound of formula (I)according to claim 1, capable of being used for protecting thepropagation material of a plant, optionally for protecting a seed.
 12. Acompound of formulae (IVa) and/or (IVb),

in which R², R³, R⁴ and R⁵ independently of one another representhydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆-alkyl,C₁-C₆-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₁-C₆-alkoxy,C₁-C₆-haloalkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio,C₁-C₆-alkylsulphinyl, C₁-C₆-haloalkylsulphinyl, C₁-C₆-alkylsulphonyl,C₁-C₆-haloalkylsulphonyl, C₁-C₆-alkylamino, N,N-di-C₁-C₆-alkylamino,N—C₁-C₆-alkylaminocarbonyl, N—C₃-C₆-cycloalkylaminocarbonyl or(C₁-C₃-alkoxy)carbonyl.
 13. A compound of formulae (Va) and/or (Vb) inwhich

X¹ represents halogen, cyano and C₁-C₄-haloalkyl, and Z² representshalogen, cyano, nitro or optionally substituted C₁-C₆-haloalkyl,C₁-C₆-alkylthio, C₁-C₆-halo alkylthio, C₁-C₆-alkylsulphinyl,C₁-C₆-haloalkylsulphinyl, C₁-C₆-alkylsulphonyl,C₁-C₆-haloalkylsulphonyl, and Z³ represents hydrogen or optionallysubstituted C₁-C₆-alkyl, C₁-C₄-alkenyl, C₁-C₄-alkynyl, C₁-C₆-haloalkyl,and Y represents optionally substituted C₁-C₆-alkyl.